Protective Effect of Adenosine in Feline Model of Acute Myocardial Ischemia-Reperfusion

BACKGROUND: Reestabilshment of blood flow is a standard therapeutic modality to salvage the myocardium at risk in an acute phase of myocardial infarction. However, there are significant evidences that reperfusion per se may injure the potentially viable myocardium, and a number of pharmacological agents were tried to reduce this reperfusion injury. Adenosine, an endogenous vasodilator, is suggested to reduce repergusion inury. To evaluate the myocardial protective effect of adenosine, magnetic resonance spectroscopy with superscript P was applied to feline model of acute myocardial ischemia-reperfusion, as well as pathological examination. METHODS: Effects of adenosine on the recovery of high energy phosphorous metabolites during 90 minutes of reperfusion period following 90 minutes of left anterior descending coronary artery ligation were assessed by31P spectroscopy in 27 cats(10: control group, 8: adenosine I group, 9: adenosine II group). In adenosine groups 0.2 mg/kg/min of adenosine was infused intravenously for 90 minutes from 30 miniutes before reperfusion in group I, and from just before reperfusion in group II. The experiments were performed on a 4.7 T/30 cm Biospec MRS/MRI system and the MR signals were obtained by using inner-diameter 1.5 cm-sized doubly tuned surface coil. The size of the spectral peaks was measured by area integration method. RESULTS: 1) Phosphocreatine(PCr) decreased rapidly with progression of ischemia, and recovered in reperfusion period in each group. PCr values in the reperfusion period were significantly higher in adenosine group than those in control group, although there was no difference between adenosine group I and II. 2) ATP decreased with progression of ischemia, and recovered in reperfusion period in each group. ATP values in the reperfusion period were significantly higher in adenosine groups than those in control group, byt there was no difference between adenosine group I and II. 3) pH decreased uniformly with progression of ischemia and recovered in reperfusion period, showing no difference between control and adenosine groups. 4) PCr/ATP ratio, representing the potential of oxidative phosphorylation, dereased with progression of ischemia and increased in reperfusion period. PCr/ATP ratio showed no difference between control, adenosine I and II groups. 5) Risk area/left ventricle ratio was not different in control and adenosine groups. Infarct size/risk area and infarct size/left ventricle ratios were smaller in adenosine II than those in control group. Howerver no significant diffence was noticed between adenosine I and control, and between adenosine I and II group. CONCLUSION: Intravenous infusion of adenosine showed the tendency of reducing the infarct size in the feline model of acute myocardial ischemia-reperfusion, and adenosine could improve significantly the recovery of high energy phosphate metabolites. This myocardial pretective effect of adenosine is considered to be present mainly in the reperfusion period.

The thrombolytic effect of lumbrokinase is not as potent as urokinase in a rabbit cerebral embolism model

The purpose of the present study is to determine whether lumbrokinase has an in vivo thrombolytic effect in a rabbit cerebral embolism model. In our previous studies, we found that lumbrokinase, an extract from Korean earth worms, has a strong in vitro fibrinolytic effect without the presence of plasminogen and significant in vivo thrombolytic effects of lumbrokinase in a rat human-clot-induced cerebral embolism model. We established the cerebral embolism model in rabbits by injecting a piece of human clot into the internal carotid artery via the external carotid artery and confirmed the occlusion with angiography. Twenty one rabbits were divided into three groups and 5cc of saline, urokinase of 50,000 u/ml, and equipotent LK were injected intraarterially for 30 minutes into each group of 7 animals. Ten minutes after the end of infusion, an angiogram was performed to confirm the recanalization. Clot lysis occurred in one, six, and one animals in the saline, urokinase and lumbrokinase treated groups respectively. With regard to its in vitro effect, lumbrokinase is not as potent in vivo. Further investigation should be performed to determine the cause of its weakened in vivo effect and to develop a method to potentiate it.

Effect of adenosine on recovery of phosphorous metabolites in acute myocardial ischemia-reperfusion : In vivo P MR spectroscopic assessment in cats

BACKGROUND: To evaluate the metabolic and pathological changes associated with myocardial ischemia-reperfusion, magnetic resonance spectroscopy with 31P was applied as well as pathological examination. METHODS: Effect of adenosine on the recovery of high energy phosphorous metabolites during the reperfusion period following 90 minutes of left anterior descending coronary artery(LAD) ligation was assessed by 31P spectroscopy in 13 cats(8 : control group, 5 : adenosine group). In adenosine group 0.2 mg/kg/min of adenosine was infused intravenously for 90 minutes from 30 minutes before reperfusion. The experiments were peformed on a 4.7 T/30cm Biospec MRS/MRI system(Bruker, Switzerland) and the MR signals were obtained by using innerdiameter 1.5 cm sized doubly tuned surface coil. The size of the spectral peaks was measured by area integration method. RESULTS: In control group, high energy phosphorous metabolites decreased continueously during the ischemic period revealing the lowest values at the end of the periods : 17.0% for PCr and 24.0% for ATP, PCr depleted below 50% of the baseline level immediately after the LAD ligation and ATP, after 15 minutes of ischemia. Therfore the depletion rate was faster in PCr change than in ATP. The recovery of the PCr and ATP occurred after reestablishment of blood flow showing, for example, 43.3% and 36.3% of the baseline levels after 10 minutes of reperfusion. After infusion of adenosine, there was a tendency of higher recovery rates of high energy phosphates than in control group. Recovery rates of PCr and ATP after 90 minutes of reperfusion, were 28.2%, 11.2% in control group and 38.3%, 18.6% in adnosine group, respectively. In adenosine grop, relative sizes of infarction were not statistically different from those of control group. CONCLUSIONS: 31P MRS can be used for in-vivo assessment of the changes of high energy phosphorous metablites concerning acute myocardial ischemia and reperfusion. Adenosine infusion improves the recovery of ATP and PCr during the reperfusion period following acute ischemia.