https://www.internationaljournalofcardiology.com/article/S0167-5273(96)02854-9/pdf

Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options

Background The role of oxidant stress in cardiac ischemia/reperfusion injury in humans remains controversial. This is due, in part, to the limitations of available indices of oxidant stress in vivo. Isoprostanes are stable, free radical–catalyzed products of arachidonic acid. We assessed their formation in patients undergoing coronary reperfusion via percutaneous transluminal coronary angioplasty (PTCA). Methods and Results We developed specific, mass spectrometry assays for two structurally distinct F2 isoprostanes, 8-epi-PGF2α and IPF2α-I. Urine samples for isoprostane determination were collected in patients undergoing coronary arteriography (n=11), elective PTCA (n=15), and angiography after thrombolysis for acute myocardial infarction (MI) (n=10). Urinary levels (pmol/mmol creatinine) of both isoprostanes were markedly increased from baseline in the first 6 hours after PTCA for acute MI (105±17.8 versus 230±66 for 8-epi-PGF2α [P=.009] and 466±91 versus 833±153 for IPF2α-I [P=.001]) and returned towar...

Increased formation of the isoprostanes IPF2alpha-I and 8-epi-prostaglandin F2alpha in acute coronary angioplasty: evidence for oxidant stress during coronary reperfusion in humans

Background N-acetylcysteine (NAC) has been shown to potentiate the effects of nitroglycerin (NTG) and to have antioxidant activity. This is the first study to assess the safety and effect of NAC in the treatment of evolving acute myocardial infarction (AMI). Methods and Results Patients with AMI received either 15 g NAC infused over 24 hours (n=20) or no NAC (n=7), combined with intravenous NTG and streptokinase. Peripheral venous plasma malondialdehyde (MDA), reduced (GSH) and oxidized (GSSG) glutathione concentrations, and rate of reperfusion (using continuous ST-segment analysis) were measured. Cardiac catheterization was performed between days 2 and 5. No significant adverse events occurred. Less oxidative stress occurred in patients treated with NAC than in patients not receiving NAC (GSH to GSSG ratio 44±25 versus 19±13 at 4 hours, P<.05). NAC concentration (mean 172±79 μmol/L at 4 hours) was correlated to GSH concentration (P=.006). MDA concentrations were lower (P=.001) over the first 8 hours of t...

N-Acetylcysteine in Combination With Nitroglycerin and Streptokinase for the Treatment of Evolving Acute Myocardial Infarction Safety and Biochemical Effects

BACKGROUNDFree radicals and lipid peroxidation have been suggested to play an important role in the pathophysiology of myocardial reperfusion injury. The purpose of the present study was to monitor myocardial malondialdehyde (MDA) production as an index of lipid peroxidation during ischemia-reperfusion sequences in patients undergoing elective coronary bypass grafting. There has been a lot of debate on the role of xanthine oxidase as a potential superoxide anion generator and thus lipid peroxidation in human myocardium. To evaluate the activity of xanthine oxidase pathway, we measured the changes in the transcardiac concentration differences in adenosine, inosine, hypoxanthine, xanthine, and uric acid.METHODS AND RESULTSThe coronary sinus-aortic root differences (CS-Ao) of MDA, oxypurines, and nucleosides were measured by a recently developed ion-pairing high-performance liquid chromatographic (HPLC) method. Fifteen patients were included in the study, and 13 of them demonstrated a more than 10-fold incre...

Myocardial release of malondialdehyde and purine compounds during coronary bypass surgery.

Post-treatment with N-acetylcysteine ameliorates endotoxin shock-induced organ damage in conscious rats.

Free-radical generation during angioplasty reperfusion for acute myocardial infarction

Between October 1991 and March 1993, 281 consecutive patients underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receive either intermittent cold (Group I-144 patients) or continuous warm (Group II-137 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of peri-operative myocardial infarction, blood loss, need for circulatory support, post-operative neurological deficit, or duration of intensive care or hospital stay. However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group II patients. There was greater transmyocardial oxidative stress in Group I patients, as evidenced by a significant rise in oxidised glutathione in coronary sinus blood on myocardial reperfusion. Also, the serum CKMb isoenzyme level 2 h post-operatively was significantly raised in Group I patients, although this difference had disappeared by the day after surgery. In conclusion this preliminary report suggests that continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with standard hypothermic techniques in patients undergoing coronary artery surgery.

A prospective randomised study of continuous warm versus intermittent cold blood cardioplegia for coronary artery surgery: preliminary report.

OBJECTIVE To evaluate which Doppler transmitral velocity indices of left ventricular diastolic function change with alteration of left ventricular filling pressure. METHODS Twenty-two patients undergoing coronary artery bypass surgery. The effect of fluid loading on indices derived from the transmitral Doppler waveform, recorded by a trans-oesophageal echocardiography, was evaluated using a generalised linear statistical model. RESULTS E-wave maximum velocity, E-wave acceleration time and slope, E-wave deceleration slope, A-wave maximum velocity and E/A wave maximum velocity ratio showed significant changes after alterations in left ventricular filling pressure. E-wave deceleration time and E-wave maximum velocity/time velocity integral showed no significant change after fluid loading. CONCLUSION Several commonly used Doppler derived indices of left ventricular diastolic function are significantly affected by changes in filling pressure of the left ventricle. This may limit the usefulness of the Doppler method for serial assessment of diastolic function when the left ventricular filling pressure has changed between assessments. Only the E-wave deceleration time did not show significant changes and might be a useful Doppler index for the serial measurement of left ventricular compliance but this needs to be confirmed with haemodynamic measurements.

Transmitral Doppler assessment of left ventricular diastolic function during coronary artery bypass surgery.

Differential Free Radial Activity (FRA) after Sucessful and Unsucessful Thrombolytic Reperfusion in Acute Myocardial Infarction

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Free-radical generation during angioplasty reperfusion for acute myocardial infarction

A prospective randomised study of continuous warm versus intermittent cold blood cardioplegia for coronary artery surgery: preliminary report.

Transmitral Doppler assessment of left ventricular diastolic function during coronary artery bypass surgery.

Differential Free Radial Activity (FRA) after Sucessful and Unsucessful Thrombolytic Reperfusion in Acute Myocardial Infarction