Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia

Masters, Thomas N.; Harbold, Norris B.; Hall, Donald G.; Jackson, Robert D.; Mullen, Donald C.; Daugherty, Harry K.; Robicsek, Francis

doi:10.1016/0002-9149(76)90396-9

Cited by 32 publications

(7 citation statements)

References 25 publications

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“…This observation confirmed results reported by Masters et al, 8 who used MP (40 mg/kg). However, no significant differences were noted in the degree of depression of AP between the untreated and MPtreated groups in the pre-occlusion (untreated: 119 ± 5; MP-treated: 121 ± 3) or the post-occlusion (untreated: 112 ± 3 at 5 minutes to 104 ± 5 at 120 minutes; MP-treated: 108 ± 4 at 5 minutes to 103 ± 6 at 120 minutes) periods.…”

Section: Hemodynamic Parameterssupporting

confidence: 92%

Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia.

Kennett¹,

Weglicki²

1978

Circulation Research

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SUMMARY Myocardial ischemia was produced for 2 hours by coronary ligation in 11 dogs pretreated with methylprednisolone (MP, 30 mg/kg). Myocardial blood flow (MBF) was measured with microspheres (IS fun) in each tissue sample used for enzymatic analysis. Homogenates of these tissue samples were separated by ultracentrifugation into lysosome-rich and microsomal fractions and were analyzed for JV-acetyl-/?-glusosaminidase (NAGA), /}-glucuronidase (/?-gluc), rotenone-insensitive-NADH-cytochrome c reductase (RINCR), and cytochrome oxidase. The enzymatic data from centrifugal fractions were grouped according to MBF values for statistical analysis of inter-group effects of ischemia. Significant losses (P < 0.001) of NAGA and /?-gluc were seen in all MP-treated lysosome-rich particulate fractions that were isolated from zones demonstrating MBF values less than 25% of control (L-ischemia). Similar significant losses (P < 0.001) of RINCR were seen in microsomal fractions from L-ischemia zones. Samples with MBF values greater than 25% but less than 75% of control (M-ischemia) also demonstrated significant decreases of lysosomal and microsomal enzymatic activity in specific fractions. When the data of the above MP-treated group were compared with the untreated control group, no significant intergroup effects of treatment with MP were observed. In addition, enzymatic data (NAGA, RINCR) were normalized prior to performing linear regression analyses; percent loss of particulate enzymatic activity was plotted against percent decrease in MBF. The effects of 2 hours of ischemia on the above biochemical parameters were comparable between untreated and MP-treated groups. Finally, when myocardial samples were grouped according to similar levels of MBF, statistical analysis using the general linear models procedure revealed no beneficial effect of MP treatment on changes in lysosomal hydrolases, microsomal RINCR, or latency of lysosomes.

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Section: Hemodynamic Parameterssupporting

confidence: 92%

Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia.

Kennett¹,

Weglicki²

1978

Circulation Research

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“…The mechanism by which glucocorticoids may benefit acutely ischemic myocardium remains conjectural. 1 hey may stabilize cell membranes, prevent or delay the release of lysosomal enzymes (33,34), stabilize the phagocytic vacuoles in infiltrating inflammatory cells, thereby reducing their heterolytic activity (16), inhibit the generation of prostaglandins and thromboxanes (35), exert other antiinflammatory actions, or increase collateral blood flow to the ischemic myocardium (36).…”

Section: Methodsmentioning

confidence: 99%

Long-Term Preservation of Ischemic Myocardium after Experimental Coronary Artery Occlusion

Maclean¹,

Fishbein²,

Braunwald³

et al. 1978

J. Clin. Invest.

169

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A B S T R A C T The results of experiments with indirect methods have suggested that various interventions reduce infarct size after coronary artery occlusion. To determine and quantify directly both the shortand long-term effects of several interventions on myocardial salvage without relying on indirect methods, the left coronary artery was occluded in 880 rats; they were then given either no treatment or one of the following interventions: (a) hyaluronidase, an enzyme that hydrolyzes interstitial glycoproteins, 1,500 National Formulary (NF) U/kg i.v. 5 min and 24 h after occlusion; (b) cobra venom factor, a protein that depletes the third component of complement, 20 U/kg i.v. 5 min after occlusion; (c) a glucocorticoid: hydrocortisone, 50 mg/kg i.v. 5 min after occlusion; or the fivefold more potent methylprednisolone (MP): (i) 50 mg/kg i.v. 5 min after occlusion or (ii) 50 mg/kg i.v. 5 min after occlusion followed by 50 mg/kg i.m. 3, 6, and 24 h after occlusion; or (d) reserpine, an agent that depletes the heart of catecholamines, 0.5 mg/kg i.m. once on each of the 3 days before occlusion. The animals were sacrificed either 2 days after occlusion, i.e., at the time of peak necrosis, or after 3 wk, i.e., after the infarct was completely healed. The amount of preserved myocardium was then assessed by two independent techniques: planimetric measurement of serial histologic sections and creatine kinase activity of the whole left ventricle. The amount of normal myocardium preserved at 21 days postocclusion was significantly increased, by 22.3±7.8% (P < 0.025) after the administration of hyaluronidase, by 25.3 ±5.8% (P < 0.005) after cobra venom factor, by 14.5 ±6.9% (P < 0.05) after hydrocortisone, by 20.8±8.2% (P < 0.025) after the single dose of MP, by 20.9±3.9% (P < 0

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“…The study by Masters et al 17 indicated the beneficial effect of methylprednisolone, 40 rag. kg-~, on carbohydrate metabolism maintaining the generation of energyproducing substrates in acute myocardial ischacmia.…”

Section: Discussionmentioning

confidence: 99%

Effect of high-dose of methylprednisolone on tourniquet ischaemia

et al. 1988

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Pneumatic tourniquets are widely used tbr limb surgery and facilitate intravenous regional anaesthesia. The extremity below the tourniquet becomes ischaemic, resulting in respiratory and metabolic acidosis, and skeletal cell damage) ,2 Biochemically, ischaemia and hypoxia are very' similar to shock; a primary metabolic abnormality is a rapid and considerable reduction in the aerobic production of energy)Massive doses of eorticosteroids, including methylprednisolone, have been found to have beneficial effects in different shock states ~6 The mechanism for the beneficial effects has not been clearly determined, but several hypotheses have been proposed. These include a cell membrane stabilizing effect, 7 reducing the liberation of vasoactive substances, ~ a direct metabolic effect, 9 and a vasodilative effect. ~0 The purpose of this study was to investigate, using a dog model, whether a corticosteroid such as methylprednisolone could attenuate the pathophysiological changes due to tourniquet-induced ischaemia. MethodsSeven large mongrel dogs weighing 23-35 kg were used for this study. The dogs were anaesthetized with pentobarbitone 30 rag. kg -1 IV. The trachea was intubated in order to assure an adequate airway, and then allowed to breathe spontaneously.IV catheters, 16 gauge, were placed in bath hind legs tbr venous access, and control venous blood samples were drawn. Identical paediatric size tourniquets were applied to the thigh of both hind legs and connected via a Y connector to a Shook tourniquet unit. Two 20 ml aliquots of venous blood were drawn from each dog's foreleg. Methylprednisolone, 3 mg'kg -I body weight, was dissolved in one of these samples of blood as a vehicle. The tourniquets were then simultaneously inflated to 600 mmItg. Blood with methylprednisolone was then injected into one of the tourniquet-occluded legs. The other 20 ml of autologous blood without methylprednisolone was injected into the opposite leg.Venous blood samples were taken from both legs at 30, 60, and 120 rain after tourniquet inflation. At 120 rain, after blood sample collection, the tourniquets were deflated, and samples were taken at 5 and 30 rain after tourniquet release.CAN J ANAESTH |98S / 35:5 t pp4~-8

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Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia

Cited by 32 publications

References 25 publications

Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia.

Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia.

Long-Term Preservation of Ischemic Myocardium after Experimental Coronary Artery Occlusion

Effect of high-dose of methylprednisolone on tourniquet ischaemia

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