Letter to the Editor Effect of N-Acetylcysteine And

Indian J Physiol Pharmacol 1999; 43 (4): 518-520

LETTER TO THE EDITOR

EFFECT OF N-ACETYLCYSTEINE AND SODIUM NITRITE ON MYOCARDIAL REPERFUSION INJURY

Sir,

(Received on May 22, 1999)

Results of experimental studies suggest India). Heart was suspended in pericardial the involvement of oxygen free radicals cradle after left sided thoracotomy at fourth (OFR) in myocardial reperfusion injury 0, intercostal space. A polythene catheter 2). Ischemia is known to deplete endogenous (1.5 mm inner diameter) was placed in the antioxidants like superoxide dismutase, left ventricle through apex t~ [ecord glutathione, catalase 0, 2) and makes ventricular pressure changes on Grass 16 myocardial, cell vulnerable to oxygen free channel polygraph (Model 79D, USA) by radical (OFR) induced damage 0, 2). OFR using Gould pressure transducer. Heart rate can damage endothelial cells at the time of and ST segment changes were monitored in reperfusion (3). Endothelial cells synthesise standard limb leads on BPL (India) and form nitric oxide which is endothelium, electrocardiograph. Another two catheters derived relaxation factor (4). Acidified were placed in the left atrium for infusion sodium nitrite (Na Oz) at pH-2 forms nitric of saline, drug or acidified N aNOz' Left oxide (5) which can inactivate superoxide anterior descending (LAD) coronary artery radicals (5, 6). N-acetylcysteine (NAC) is was dissected free above first diagonal known to replenish glutathione stores, branch and below the origin of left increase superoxide dismutase activity, circumflex artery. Duration of LAD coronary scanvenge hydroxyl radicals and interfere artery occlusion was 90-min. Following with autocatalytic lipid peroxidation (7, 8). completion of occlusion, reperfusion of the In our previous studies we have shown the myocardium was initiated by removing the individual effects of NAC and NaNOz on vessel occludeI'. No attempt was made to myocardial reperfusion injury (9, 10). resuscitate the animals that developed Present study was designed to examine the ventricular fibrillation at the time of combined effect of NAC and NaNOz on reperfusion and these anim als were myocardial reperfusion injury in dogs excluded from the study. following 90 min of ischemia and 4 hI's of reperfusion. Animals were divided into two groups and each group consisted of six animals. In Adult male mongrel dogs weighing 10 to control group (Gr. I), animals underwent 15 kg were anaesthetised with iv 90 min of LAD occlusion followed by pentobarbital sodium (40mg/kg, BW), reperfusion with saline (0.9% Nacl, 115 ml) intubated and ventilated with room air by at the end of ischemia upto 4 hI's through using positive pressure ventilator (INCO, left atrium. NAC and NaNOz treated Indian J Physiol Pharmacol 1999; 43(4) Letter to the Editor 519 animals (Gr. II) received loading dose of It is evident from results (Table 1) NAC (250 mglkg) at the time of reperfusion LVEDP following 90 min of ischemia was upto an hour followed by total maintenance significantly higher in both the groups in dose (70 mg/kg) through left artium for comparison to the pre-CAO. Reperfusion in remaining 3 h. Acidified NaNOz (0.30 moll saline treated animals had no significant L HCL, pH-2) was also infused along with effect on LVEDP in comparison to 90 min NAC at the time of reperfusion for 4h. Both Post-CAO. Infusion of NAC and NaNOz at the drugs were infused by using different the time of reperfusion significantly lowered catheters palced in the left atrium. Infarct the LVEDP. However, LVSP remained size following ischemia and reperfusion was unchanged following ischemia and quantified by earlier described method (9). reperfusion. Combined infusion of NAC and In brief, unstained portions of myocardium NaNO z at the time of reperfusion by Evans blue represented zone at risk and significantly decreased the percent left unstained portions by triphenyl-tetrazolium ventricular necrosis in comparison to saline chloride showed infarcted zone. Lipid treated animals. MDA levels in the infarcted peroxidabon in the zone at risk and zone were comparatively lower in group II. infarction was measured by the method of Kartha and Krishnamurthy (11). Values of In our earlier studies we have shown lipid peroxidation were expressed in the that individual treatments with either NAC terms of malondialdehyde (MDA)/g wet or NaNOz at the time of reperfusion tissue weight.after taking molar extinction following 90 min of ischemia had no effect

TABLE I: Left ventricular systolic pressure (LVSP), End diastolic pressure (LVEDP), % Necrosis and Malondialdehyde (MDA) levels following ischemia and reperfusion.

Experimental Parameters Pressure % Left ventricular MDA Groups (mm of Hg) necrosis (n mol/g tissue)

Pre·CAO Post- CAD Post - reperfusion (90 min) (4 h)

LVSP 164.4 ±10.45 154.66±2.17 148.1±2.78 12.6±1.5 21.72± 2.14 Saline reperfused LVEDP 2.70±1.08 19.88±3.3 15.62±4.76 (n = 6)

II LVSP 158.6±4.6 151.2±2.6 155.2±1.96 5.74±1.85* 12.51± 3.4* NAC + NaN02 treated LVSDP 2.8±1.76 18.8±2.6* 5.24±2.60* (n = 6)

YOGESH TRIPATHI,* B. M. HEGDE,** Y. S. RAI*** AND C. V. RAGHUVEER***

Departments of ¥'Physiology, """Medicine, ''k%'Y'Surgery and "'*''''''Pathology, Kasturba Medical College, Mangalore - 575 001

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