The Clinical And Experimental Study On Adrenomedullin In Acute Myocardial Infarction

Adrenomedullin (ADM) is a newly discovered important vasorelaxant peptide.It plays an important role in the development of many diseases. But little do we knowabout its pathophysiological actions in acute myocardial infarction (AMI). So wemade this clinical and experimental study in order to investigate thepathophysiological role and its mechanisms of ADM in AMI.It is not known whether or not thrombolysis, which is an important therapy forAMI, can effect. It is also not reported about the effect of infarction site onplasma ADM, the reation of plasma ADM to left ventricular cardiac function and toanother importan neurodocrine hormone atrial natriuretic peptide (ANP). Therforein the clinical researh we have studied these problems. In terms of reported studies,we hypothesis that increased plasma ADM in diseases is a compensable reaction tothe pathophysiological alterations in order to protect the body against the diseases tofurther deteriorate. And the radical pathological changes in AMI are the myocardialinjury and infarction and the dysfunction of cardiac contraction and relaxaioninduced by the former But little do we know about this protective effect and itsmechanisms. Consequentially, in the experimental study we have investigated theprotective effect of ADM on myocardial injury and cardiac dysfunction by means ofADM perfusion in rat myocardial injury model induced by isoproterenol. We havealso studied the compensable protective mechanisms of ADM on the level ofsubcellular orpanelles and recepors by means of investigating the effect of ADM onthe aIteratons in cardiac sarcoplasmic reticulum (SR) Ca～(2+) uptake and Ca～(2+) releaseactivities as well as in SR Ca～(2+)-ATPase activities and ryanodine recetors.The major results of the present study are in the following.l. Plasma concentrations of ADM wer significantly increased immediately afteronset of AMI and gradally reached to the peak value at the 24～(th) hour. Then theybeqan to decrease but were higher than those of control subjects till at the 72～(nd)hour2. PIasma concentfations of ADM wer significantly higher in those with congeStiveheart fa1ure than in those withou congeStive heart fai1ure during the 2 Weestime of Observ8tion.3. Plasma concentrations of ADM in patients with successful thrombolysis had adecrase trend Wared ch those in patients ch unsuccessful thrombolysis.The former was significantly lOwer than the latter at the 72nd hou.4. Plasma concendons of ADM in inferior infarction wee generally lowe than inanterior infaredon. The difference bdeeen them was significam at the 48th and72nd hour5. Plasma concentrations of ADM had a significant nwive corred ation wth the leftventricular ejeCtion fration at the 24th hour.6. There was a significan correlation between plasma concentrations of ADM andM at 24m W. But they had differnt dynamical alterations. ADM increasedcontinuously and reached the peak value gradually whereas ANP rcached thepeak value immediately after onset of AMI and shmpIy decreased to the leveI ofcontroI subjeCts at the I2th hour aller that it began to eIevae s1owlyThe present clinical study demonstrates tha plasma ADM is acivaedimmediately aller onset of AMI and plasma concenrations of ADM have a very closerelationship whh the status of cardiac funCtion, Which indicates tha the increandplasma ADM is a compensable proteCtive reaCtion tO the disabled cardiac funCtion. Itcan improve the cardiac dysfunCtion of patients with AMI by means of its bioIogicalactions such as natriuresis, diuresis, and vasorelaxaion. Because successfulthrombolysis theraPy can save the critical myoCardia1 and imProve tbe CardiacfunCtiory plasma concentrations of ADM therefore decrease. Plasma concelltrations ofM are higher in amerior infaCtion than in inferior infaforion indicates tha the siteof M secretion is in the ventricles, becanse inferior infarCtion usually includesathal infawtiOn but atrial perhaps don'...