Vane blood-bathed technique reveals the significance of adrenergic reaction in myocardial infarction.

Using the blood-bathed technique of Vane we induced acute coronary occlusion in the dog and subsequently detected adrenaline release into the circulatory system, determined the rate of release and documented its significance for induction of cardiac arrhythmias. In the intact anesthetized dog, adrenaline excess of the magnitude released after coronary occlusion was sufficient to injure the healthy myocardium and to induce unfavorable metabolic systemic alterations. Subsequently, clinical research has documented that a serious clinical course of acute myocardial infarction is associated not only with enhanced excretion of catecholamines but also with augmentation of plasma renin activity and aldosterone levels.

Effects of vitamins C and E on the outcome after acute myocardial infarction in diabetics: a retrospective, hypothesis-generating analysis from the MIVIT study.

Background: There is significant evidence that reactive oxygen species play an important role in endothelial dysfunction, ischemia/reperfusion injury as well as in the pathogenesis of diabetes mellitus (DM). It is also known that vitamins C and E have substantial antioxidant properties. However, clinical evidence concerning this topic is insufficient so far.

Low serum triiodothyronine in acute myocardial infarction indicates major heart injury.

Aims: In patients with acute myocardial infarction (MI), low serum triiodothyronine (T3) concentration is commonly associated with a severe clinical course. The aim of this prospective study was to investigate whether a severe clinical course in patients with low T3 is related to the magnitude of myocardial injury assessed by echocardiography.

Methods And Results: Out of 635 patients with MI we enrolled 100 consecutive patients.

L-arginine supplementation prolongs exercise capacity in congestive heart failure.

Background: In congestive heart failure (CHF), endothelial dysfunction may contribute to impairment of exercise induced vasodilatation and decreased exercise capacity. We hypothesised that administration of L-arginine, a precursor of nitric oxide (NO) and postulated antioxidant, may improve endothelium-dependent vasodilatation and exercise capacity and also exert antioxidant activity.

Aims: To investigate the effect of oral supplementation with L-arginine on exercise capacity and markers of oxidative stress in patients with mild to moderate CHF.

Release of matrix metalloproteinase-9 during balloon angioplasty in patients with stable angina. A preliminary study.

Background: Vascular wall remodeling is a major factor contributing to restenosis after angioplasty that involves migration and proliferation of vascular smooth muscle cells. The release of matrix-degrading metalloproteinases, including metalloproteinase-2 and metalloproteinase-9, facilitates remodeling. Experimental data suggest that nitric oxide (NO) decreases the activity of metalloproteinases and this may attenuate arterial remodeling after balloon injury.

Elective coronary angioplasty with 60 s balloon inflation does not cause peroxidative injury.

Background: The aim of this study was to evaluate the ongoing controversial issue of whether ischemia/reperfusion during elective coronary angioplasty evokes myocardial peroxidative injury.

Design: We measured indicators of free radical damage to lipids (free malondialdehyde) and proteins (sulphydryl groups) in coronary sinus blood in 19 patients with stable angina who were undergoing elective angioplasty for isolated stenosis of the proximal left anterior descending coronary artery. Ischemia induced by 60 s balloon inflations was confirmed by lactate washout into coronary sinus after deflation, with immediate and 1 min samples.

Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris.

We assessed the effects of L-arginine (an endogenous precursor of nitric oxide) on the magnitude of exercise-induced QT dispersion in patients with coronary artery disease. The study had a randomized double-blind cross-over design. Twenty-five patients with stable coronary artery disease underwent two separate exercise tests: after oral administration of L-arginine (6 g/24 h for 3 days) or placebo.

Positive and negative outcomes of L-arginine therapy in cardiovascular diseases.

The author reviews controlled clinical investigation on the effectiveness of L-arginine in cardiovascular diseases. Positive results were observed in hyperlipidemic subjects and in patients with a critical stage of the peripheral arterial occlusive disease. Patients with stable ischemic heart disease responded to L-arginine to some extent, while results of L-arginine therapy in congestive heart failure are inconsistent.

Effect of early captopril treatment on blood adrenaline levels in acute myocardial infarction (the substudy of ISIS-4). International Study of Infarct Survival-4.

Of patients with acute myocardial infarction eligible for the International Study of Infarct Survival-4, randomized to captopril (n = 30) or placebo (n = 33), the captopril group had a significant decrease in blood adrenaline on day 3 compared with baseline values. Results suggest that suppression of sympathetic activity contributes to the beneficial effects of treatment with angiotensin-converting enzyme inhibitors in the early phase of acute myocardial infarction.

Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris.

A randomized, double-blind, placebo-controlled study in patients with clinical symptoms of stable angina pectoris and healed myocardial infarction (n = 22) has shown that oral supplementation with L-arginine (6 g/day for 3 days) increases exercise capacity (tested on a Marquette case 12 treadmill according to the modified Bruce protocol). Results suggest that the inefficient L-arginine/nitric oxide system contributes to limitation of myocardial perfusion and/or peripheral vasodilation during maximum exercise in patients with stable angina pectoris.

Effects of antioxidant vitamins C and E on signal-averaged electrocardiogram in acute myocardial infarction.

Experimental studies indicate that oxygen-free radicals contribute to ischemic myocardial damage and affect electric properties of cellular membranes. We hypothesize that an association exists between an oxygen-free radical-induced component of myocardial ischemic injury and altered electric function that underlies the genesis of ventricular late potentials in the course of myocardial infarction. If so, antioxidant vitamins C and E may prevent alterations in the signal-averaged electrocardiogram (SAECG).

Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction.

Clinical studies suggest that neutrophil activation during acute myocardial infarction (MI) aggravates tissue injury. Activated neutrophils are an important source of oxygen free radicals (OFR), the injurious effects of which are counteracted by endogenous antioxidants. We have previously shown in healthy subjects that supplementation with antioxidant vitamins C and E suppresses OFR production by isolated neutrophils assayed by chemiluminescence (CL).

Inhibitory effect of vitamins C and E on the oxygen free radical production in human polymorphonuclear leucocytes.

Beneficial effects of dietary supplementation with antioxidant vitamins are attributed mainly to the influence upon lipid metabolism, endothelial and vascular functions. Their effect upon leucocyte oxygen free radical producing capacity has not been investigated. In 13 healthy volunteers we examined the influence of oral supplementation with vitamins C and E (aa 600 mg per day for 14 days) upon leucocyte oxygen free radical production estimated by lucigenin-amplified chemiluminescence in isolated leucocytes stimulated with arachidonic acid.

Platelet adhesion is related to heart rhythm disturbances in the acute phase of myocardial infarction.

This study examines the relationship between platelet adhesion, aggregation and the occurrence of heart rhythm disturbances in 43 consecutive patients (mean age 58) admitted to a coronary care unit with acute myocardial infarction. Blood for platelet studies was taken prior to institution of any medication and heart rhythm was monitored (Holter) for 24 h after admission. The control group consisted of 22 healthy subjects (mean age 55 yr).

Effect of magnesium on myocardial damage induced by epinephrine. Ultrastructural and cytochemical study.

Magnesium ion is involved in energy metabolism, transport of ions and control of intracellular Ca2+. Catecholamines, intensify cellular Mg2+ depletion and the detrimental effects of catecholamine excess and Mg2+ deficiency are mutually enhancing in the myocardium. To investigate whether Mg2+ supplementation protects the myocardium against damage induced by catecholamines, we examined the ultrastructure and the ultracytochemical localization of Ca2+ in the myocardium of rabbits infused with epinephrine (1 microgram/kg/min intravenously for 2 hours), in rabbits infused simultaneously with epinephrine and MgSO4 (50 mg/kg, intravenously) and in saline-infused controls.

Effect of adrenaline on cardiac force-interval relationship.

Objective: The aim was to test the hypothesis that adrenaline affects the force-interval processes.

Methods: The force-interval processes were studied in eight guinea pig papillary muscles (isometric force) and five anaesthetised dogs with atrioventricular block (maximum rate of rise of left ventricular pressure, LVdP/dtmax). The contractility indices were measured during pacing sequences in which a steady state was interrupted after a variable interval by a premature beat followed by an immediate return to the steady state.

NG-monomethyl-L-arginine increases platelet deposition on damaged endothelium in vivo. A scanning electron microscopic study.

There is increasing evidence that nitric oxide (NO) synthetized in vascular endothelium and in platelets by NO synthase influences vascular tone, down regulates platelet function and platelet-vessel wall interaction both in vitro and in vivo. We investigated the effect of a NO synthase inhibitor, NG-mono-methyl-L-arginine (L-NMMA, 100 mg/kg iv) on platelet-endothelial cell interaction in rabbit arteries ex vivo using scanning electron microscope (SEM). The effect of L-NMMA was examined on intact endothelium and on that damaged by arterial constriction.

Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig.

A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, we studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress.

Stress-induced injury of pig myocardium is accompanied by increased lipid peroxidation and depletion of mitochondrial ATP.

The aim of the study was to investigate the mechanisms of myocardial lesions induced by stress in conscious, intact pigs. The animals were subjected to 24 h immobilization, controls were kept in normal conditions. The pigs were killed by electric shock and exsanguination.

Nisoldipine inhibits lipid peroxidation induced by coronary occlusion in pig myocardium.

Study Objective: The aim was to investigate the effect of the Ca++ channel blocker nisoldipine on the content of lipid peroxidation products in pig myocardium after acute coronary occlusion.

Design: Open chest pigs were subjected to the occlusion of the left anterior coronary artery (LAD) with or without nisoldipine. After 30 min ischaemia, myocardial samples were taken from the ischaemic area and from the non-ischaemic posterior wall of the left ventricle for determination of lipid peroxidation products.

Increased activity of circulating polymorphonuclear leukocytes in acute myocardial infarction.

Acute myocardial infarction results in an increased sensitivity of circulating polymorphonuclear leukocytes to ex vivo aggregation. This increase was prevented by pretreatment of leukocytes with BW755, but not with aspirin, suggesting that the activation of blood leukocytes in infarction is due to a stimulation of cellular lipoxygenase.

Effect of nisoldipine on stress-induced myocardial damage in the conscious pig.

1. The effect of the calcium channel blocker nisoldipine on the myocardial content of lipid peroxidation products (malondialdehyde (MDA), conjugated double bonds (CDB), fluorescent end-products (RF) and mitochondrial adenine nucleotides) was investigated in conscious pigs (n = 14) subjected to 24 h of immobilization stress. Histoenzymatic and electron microscopic studies of the myocardium were also performed.

Apparent inosine uptake by the human heart.

Although inosine has been used clinically to support the myocardium, no data are available on the fate of exogenous inosine in the human heart. We therefore infused six patients, catheterised for coronary angiography, with inosine (5 mg.kg-1.

Evidence for increased lipid peroxidation in the non-ischaemic portion of the heart with coronary occlusion.

Lipid peroxidation products, malondialdehyde (MDA), conjugated double bonds (CDB), and fluorescent end products (RF), were measured in porcine left ventricular myocardium. Myocardial samples were taken 15-20 min after left anterior descending coronary artery (LAD) ligation from ischaemic and non-ischaemic regions. Products of lipid peroxidation were also measured in the left ventricular myocardium of sham operated pigs.

Calmodulin antagonist reduces release of malondialdehyde from isolated ischemic/reperfused rat heart.

To investigate the role of Ca-calmodulin complex in the development of myocardial injury caused by ischemia and reperfusion, an isolated working rat hearts were subjected to ischemia/reperfusion with and without calmodulin antagonist, trifluoperazine (TFP 5 x 10(-7)M) in the perfusion medium. In TFP-treated hearts postischemic recovery of hemodynamic function was markedly improved and the release of LDH and malondialdehyde (MDA) significantly reduced as compared with control hearts. It is concluded that: 1) calmodulin-dependent mechanism seems to be involved in peroxidative injury of cellular membranes, 2) cardioprotective effect of TFP results at least in part from prevention of membrane damage caused by lipid peroxidation.