Protective Effects Of Anisodamine On Renal Function In Acute Inferior Myocardial Infarction Patients With Diabetic Nephropathy Undergoing Primary Percutaneous Coronary Intervention

Objective: This single blinded, placebo-controlled and randomized trialwas to evaluate the protective effects of anisodamine on renal function inacute inferior myocardial infarction (AIMI) patients with diabetic nephropathy(DN) undergoing primary percutaneous coronary intervention (PCI).Methods: From February2012to December2013, all consecutive AIMIpatients within12hours from onset of symptoms accompanying with DN inour cardiology department were enrolled. Eligible patients were randomlyassigned to receive anisodamine (anisodamine group, ANI) or placebo(control group, CON) by means of random number table. Inclusion criteria:All eligible patients were complying with standards as listed below:(1) Thediagnostic criteria of AIMI;(2) The type2diabetes diagnostic criteria;(3)Thediagnostic criteria of DN III, IV in the past;(4) Family members of patientshave signed surgical informed consent. Exclusion criteria: All eligible patientsdidn’t suffer from diseases as follows:(1) Allergic to anisodamine, anestheticor contrast medium;(2) Severe hepatic insufficiency;(3) Aortic dissection;(4)Severe renal insufficiency required dialysis treatment;(5) Cardiogenic shockrequired intra-aortic balloon pump (IABP) support;(6) Glaucoma;(7)Tachycardia arrhythmia;(8) Use of nephrotoxic drugs within one week;(9)Anticoagulant or antiplatelet contraindication;(10) Active internalbleeding;(11) Severe anemia or thrombocytopenia;(12) Pregnant or lactatingwomen;(13) Need surgical bypass treatment;(14) Not signed the surgeryinformed consent;(15) Other conditions not suitable to primary PCI oranisodamine. Patients in ANI group were given anisodamine50μg/kg bolusinjection within3minutes after randomization followed by an adjusted-dose (0.15-0.25μg/kg/min) to24hours after PCI, while patients in CON groupreceived infusion of placebo (0.9%sodium chloride) with the same volume ofANI group. Other medications: vasodilator, beta-blockade, aspirin,clopidogrel, ACEI/ARB, statins, platelet glycoprotein Ⅱ b/Ⅲ a receptorantagonist, anticoagulants and so forth were all used in accordance with thecurrent best guidelines. The primary PCI was performed by the radial or ulnarpath of the forearm and totally met the success criteria of PCI (TIMI flowgrade3). Non-ionic low-osmolar contrast medium (CM, Ultravist,370mgI/ml)was used in PCI. Intravenous hydration was given to all patients withintravenous0.9%sodium chloride at a rate of1ml/kg/hour or0.5ml/kg/hourin case of overt heart failure before the procedure and for12hours after theprocedure. The levels of Serum Creatinine (SCr) and Cystatin C (CysC) weremeasured at admission and at hour24,48,72after primary PCI. Estimatedglomerular filtration rate (eGFR) was calculated by the simplifiedmodification of diet in renal disease study equation (MDRD): eGFR=186×Serum creatinine-1.154×age-0.203(female×0.742). The incidence ofcontrast induced nephropathy (CIN) were calculated according to the SCrlevels. All data were analyzed with the aid of SPSS13.0. A P Value of lessthan0.05(2-tailed) was considered statistically significant.Results: Of the78patients enrolled,39were randomly assigned toreceive anisodamine (ANI group,30male, average age58.0±6.79years old)and39to placebo (CON group,29male, average age57.1±5.30years old).1There were no significant differences between the two groups in baselinecharacteristics, including gender distribution, mean age, body mass index(BMI), risk factors, basic heart rate before PCI, diastolic blood pressure,systolic blood pressure, random blood glucose, glycated hemoglobin, plasmaBNP, oral drugs and so on (P>0.05).2There were not significantly different in onset-to-door time, door-to-balloon time, the distribution of infarction related artery, stent implantations,hydration liquid volume, total CM consumption and so forth between the twogroups ((P>0.05)). 3The comparison on the results of renal function3.1Changes of SCrThe SCr concentrations were not significantly different between the twogroups before PCI (P=0.760). However, the SCr concentrations were lower inANI group than that in CON group at hour48and72after PCI (109.7±15.15μmol/L vs.126.1±20.81μmol/L, P<0.001),(87.2±13.86μmol/L vs.94.2±14.96μmol/L, P=0.035). To be specific, the SCr concentrations in the two groupswere significantly higher after PCI than the basic levels and the peak values ofthe two groups were both at hour48. SCr concentration at hour72returned tobaseline level (87.2±13.86μmol/L vs.86.0±12.19μmol/L, P=0.273) in ANIgroup, while in CON group, SCr level at hour72also decreased significantly,but the result was still higher than baseline (94.2±14.96μmol/L vs86.7±13.40mol/L, P<0.001).3.2Changes of CysCThe CysC concentration at admission was not significantly differentbetween the two groups (P=0.822). The CysC levels were markedly lower inANI group than that in CON group at hour24and48(1.066±0.249mg/L vs.1.199±0.259mg/L, P=0.023),(0.771±0.145mg/L vs.1.024±0.249mg/L, P<0.001). In ANI group, the CysC concentrations decreased at hour48significantly than that at hour24(0.771±0.145mg/L vs.1.066±0.249mg/L,P<0.001) and returned to the baseline (0.771±0.145mg/L vs.0.769±0.140mg/L, P=0.421). In CON group, the CysC levels decreased at hour48significantly than that at hour24after PCI (1.024±0.249mg/L vs.1.199±0.259mg/L, P<0.001), but the result was still higher than the baseline (1.024±0.249mg/L vs.0.776±0.160mg/L, P<0.001). The CysC level at hour72afterPCI decreased to the level before PCI (0.780±0.159mg/L vs.0.776±0.160mg/L, P=0.614).3.3Changes of eGFRThe eGFR at admission was also similar between the two groups(P=0.723). The eGFR were significantly higher in ANI group than that inCON group at hour24,48and72after PCI (87.9±12.43ml· min-1·1.73m-2 vs.82.4±10.06ml· min-1·1.73m-2, P=0.036),(76.9±10.28ml· min-1·1.73m-2vs.69.6±12.99ml· min-1·1.73m-2, P=0.008),(93.3±13.48ml· min-1·1.73m-2vs.82.8±11.39ml· min-1·1.73m-2, P<0.001). In ANI group, eGFRincreased significantly at hour72compared with that at hour48(93.3±13.48ml· min-1·1.73m-2vs.76.9±10.28ml· min-1·1.73m-2, P<0.001)and the result was similar to the baseline level (93.3±13.28ml· min-1·1.73m-2vs.93.9±12.94ml· min-1·1.73m-2, P=0.229). In CON group, eGFR increasedsignificantly at hour72, but still lower than baseline level (82.8±11.39ml·min-1·1.73m-2vs.95.0±14.16ml· min-1·1.73m-2, P<0.001).3The incidence of CIN between the two groupsThe incidence of CIN was17.9%(7/39) and41.0%(16/39) in ANI andCON group respectively. The incidence of CIN in ANI group was lower thanthat in CON group within72hours after the procedure (P=0.025). Dialysiswas not used in both groups.4Safety evaluationThere was a mild increase of heart rate after administration ofanisodamine (70.9±8.01bpm vs.66.1±8.13bpm, P<0.001). The peak valueoccurred after bolus of anisodamine (80.6±9.87bpm vs.66.1±8.13bpm,P<0.001), and recovered6hours later after withdrawal of anisodamine.(66.2±8.71bpm vs.66.1±8.13bpm, P=0.661). There were3cases withpalpitation,10cases with thirst and2cases with blurred vision, but all thepatients could bear the discomfort in the ANI group; all patients didn’temerge urinary retention. No malignant ventricular arrhythmia and cardiacdeath happened in the two groups.Conclusion: Intravenous infusion of anisodamine before and afterprimary PCI can alleviate the renal impairment caused by CM, reduce theoccurrence of CIN in AIMI patients with DN undergoing primary PCI safely.