Relation of absence of ST reelevation immediately after reperfusion and success of reperfusion with myocardial salvage

To examine whether resolution in ST elevation without ST reelevation immediately after reperfusion indicates successful reperfusion with myocardial salvage, we studied 40 patients who had an extensive acute myocardial infarction with early reperfusion: 24 patients had ST reelevation and 16 patients had no ST reelevation. Results indicate that (1) in the group with ST reelevation, rapid progression of myocardial damage occurs by reperfusion itself (i.e., reperfusion injury) and (2) in the group without ST reelevation, myocardial damage had already been extensive and irreversible at the time of reperfusion; thus, the absence of ST reelevation is not always a sign of reperfusion with myocardial salvage.     

Coronary surgery on the beating heart under extracorporeal circulation in high-risk patients. An acceptable compromise?

Coronary artery surgery with cardioplegia in high risk patients carries a risk of myocardial ischaemia and, without cardiopulmonary bypass, is not always technically feasible. The authors assessed an alternative, surgery on the beating heart with haemodynamic assist by cardiopulmonary bypass in 43 consecutive patients with poor left ventricular function (mean ejection fraction: 0.26), evolving myocardial ischaemia or acute myocardial infarction, old age (mean: 79.5 years) and comorbid conditions. Results were assessed mainly on clinical criteria. In addition, 9 patients had pre- and post-cardiopulmonary bypass measurements of markers of myocardial ischaemia (troponine Ic) and systemic inflammation (interleukines 6 and 10, elastase). In 6 cases, right atrial biopsy was analysed for expression of messenger ribonucleic acid coding for heat shock protein (HSP) 70; the data were compared with those of patients operated under warm blood cardioplegia. There was one cardiac death and one myocardial infarction. Myocardial conservation was confirmed by the minimal increase in troponine Ic levels and the significant increase in HSP 70 in RNA suggesting myocardial adaptation to stress. On the other hand, the minimal concentrations of mediators of inflammation were not significantly changed. In selected high risk patients, coronary revascularisation on the beating heart under cardiopulmonary bypass could be a valuable alternative. It conserves the potentially deleterious effects of cardiopulmonary bypass but peroperative global myocardial ischaemia, an important factor in the aggressivity of cardiac surgery, is eliminated.     

Cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability in isolated pig hearts after ischaemia and reperfusion

Isolated pig hearts, subsequently perfused with pig or human blood, were prepared for the cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability. Oxidant stress was associated with ultrastructural changes commonly seen following myocardial reperfusion. In addition, the precipitation of cerium perhydroxide following perfusion with physiological saline containing cerium chloride suggested the vascular endothelium and leukocytes as sources of oxidants. This was associated with rapid penetration of horseradish peroxidase through the intercellular clefts of the vascular endothelium into the interstitial space, suggesting increased vascular leakiness at these sites. The rapid penetration of horseradish peroxidase was observed at all monitored periods of reperfusion with pig or human blood. This indicates that the increased permeability occurred during the ischaemic period and continued during reperfusion. Morphological damage was greatest in pig hearts reperfused with whole human blood and this was attenuated if the blood was preabsorbed to remove antibodies prior to reperfusion. We conclude that oxidant stress was initiated during ischaemia and continued during reperfusion in this model.     

Intrathecal neostigmine, but not sympathectomy, relieves mechanical allodynia in a rat model of neuropathic pain

OBJECTIVE: In myocardial ischaemia, slow conducting capsaicin-sensitive C-fibres are activated. Apart from the mediation of pain, activation of these fibres causes release of various peptides, such as calcitonin gene-related peptide (CGRP), which is a potent vasodilator. The aim of this study was to investigate the role of CGRP in the context of myocardial ischaemia in vivo. METHODS: The left anterior descending coronary artery (LAD) was occluded during 45 min in 27 anaesthetised open-chest pigs. LAD flow, mean arterial pressure (MAP), heart rate, peak dP/dt, arterial and coronary venous concentration of CGRP was measured prior to ischaemia, and during 4 h of reperfusion. The extent of myocardial infarction was measured using staining with triphenyl tetrazolium chloride. RESULTS: Retroinfusion of CGRP (100 micrograms) into the ischaemic myocardium was associated with a more pronounced hyperaemia, and systemic hypotension, during early reperfusion. The infarct size in relation to the area at risk was not affected by CGRP or the CGRP antagonist CGRP(8-37), and averaged 67 +/- 3%. There were no changes in plasma CGRP levels during ischaemia or reperfusion. CONCLUSION: Exogenously administered CGRP can cause systemic hypotension and augments postischaemic coronary flow. In this model, no cardioprotective effect of CGRP could be proven.     

Management of heart failure complicating acute myocardial infarction

Development of heart failure complicating acute myocardial infarction is directly related to the extent of myocardial infarction and complex architectural changes defined as infarct expansion and remodeling. ACE inhibitors are an exciting class of agents that have the potentiality to prevent left ventricular dilatation, evolution of heart failure and death in the acute myocardial infarction setting. Besides, reperfusion is a important intervention that prevents infarct expansion in the early period after myocardial infarction. Early reperfusion limits expansion by infarct size reduction while late reperfusion reduces expansion independent of myocardial salvage by limiting transmural damage and improving the infarct healing. Therefore, reperfusion therapy decreases the incidence of congestive heart failure and significantly improves the prognosis of heart failure. On the other hand, the in-hospital mortality rate of cardiogenic shock, resulting from acute myocardial infarction, remains high, although primary PTCA has apparently resulted in substantial improvement in mortality of myocardial infarction shock. Thus, reperfusion treatment may be more effective in preventing rather than treating cardiogenic shock.     

Ischaemic preconditioning and cardiac surgery

OBJECTIVE: This review discusses the phenomenon of ischaemic preconditioning and its potential application to cardiac surgery. The biology of ischaemic preconditioning is explained and the more limited evidence suggesting that the human heart can be preconditioned is discussed. METHODS AND RESULTS: It is now accepted that the heart is capable of short-term rapid adaptation in response to brief ischaemia so that during a subsequent, more severe ischaemic insult myocardial necrosis is delayed-ischaemic preconditioning. The infarct-delaying properties of ischaemic preconditioning have been observed in all species studied. Five minutes of ischaemia is enough to initiate preconditioning and the protective period lasts for 1-2 h. Laboratory experiments have demonstrated that the stimulation of adenosine receptors initiates preconditioning and the intracellular signal transduction mechanisms involve protein kinase C and ATP-dependent potassium channels, although there may be some differences between species. An analysis of studies on myocardial infarction in humans has revealed that some patients reporting angina in the days before infarction have a better outcome and this may be due to the ischaemia causing preconditioning. More direct evidence has come from an investigation of patients undergoing percutaneous transluminal angioplasty in whom the ST-segment changes induced by balloon inflation were more marked during the first inflation than the second. In patients undergoing coronary artery bypass grafting the decline in ATP content during the first 10 min of ischaemia was reduced in patients subjected to a brief preconditioning protocol. CONCLUSIONS: Preconditioning is a powerful and reproducible method of protecting the myocardium from irreversible ischaemic injury. There is now evidence indicating that the human heart can be preconditioned. However, more trials are necessary in patients undergoing cardiac surgery before the role of preconditioning as a means of myocardial protection can be assessed.     

Effect of postischaemic hypothermia on the mitochondrial damage induced by ischaemia and reperfusion in the gerbil

In order to test the effect of hypothermia on mitochondrial function damage following cerebral ischaemia/reperfusion, Mongolian gerbils were submitted to 30 min bilateral carotid occlusion and 2 h of reperfusion at 37 degreesC or 30 degreesC. After normothermic (37 degreesC) ischaemia/reperfusion, significant decreases in mitochondrial state 3 (+ADP) oxygen consumption (-42.2%), complex II-III activity in synaptosomes (-31.7%) and complex IV were measured, in both free mitochondria and synaptosomes (-30.3% and -27. 8% respectively). However, following hypothermic (30 degreesC) reperfusion, both respiration rates and all enzyme activities remained at levels not significantly different from those in the sham operated controls.     

Protective effect of hyperin against myocardial ischemia and reperfusion injury

AIM: To study the protective and antiperoxidative effects of hyperin (hyperoside; quercetin-3-O-galactoside; Hyp) on myocardial ischemia/reperfusion. METHODS: The rabbit anterior descenging branch of left coronary artery was occluded for 60 min and then released to allow reperfusion for 20 min. Hemodynamics (LVP, LV +/- dp/dt) and electrocardiogram (ECG, lead II) were monitored continuously with polygraph. After reperfusion, the blood sample and myocardium were taken to assay plasma creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and cations in myocardium. Using a Langendorff system, the isolated heart of rat was initiated by ischemia for 40 min followed by 30 min of reperfusion. Malondialdehyde (MDA) contents of cardiac effluent and myocardium were measured with fluorescence spectrophotometer. RESULTS: Hyp 10 mg.kg-1 i.v. depressed changes in LVP, LV +/- dp/dtmax, ECG, plasma CPK, LDH, and cations (Ca2+, Mg2+, Na+) in myocardium induced by ischemia/reperfusion in rabbits. Hyp 10 and 100 mumol.L-1 markedly reduced the increase in MDA production in isolated rat hearts after ischemia/reperfusion. CONCLUSION: Hyp possesses a protective effect against myocardial ischemia/reperfusion injury via attenuating lipid peroxidation.     

Effect of endogenous nitric oxide on energy metabolism of rat heart mitochondria during ischemia and reperfusion

The effects of ischemia and postischemic reperfusion on the functions of the heart and its mitochondria were studied with special attention to the effect of nitric oxide (NO) by treatment of rat hearts with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or its noninhibitory isomer N(G)-nitro-D-arginine methyl ester (D-NAME). NO generated during reperfusion caused increase in coronary flow (CF), but had no effect on the left ventricular pressure (LVP) or heart rate (HR). The ATP level of the heart decreased during ischemia and was not completely restored by introduction of oxygen during reperfusion due to damage of complexes I and II of the respiratory chain of mitochondria by NO. Inhibition of the respiratory chain resulted in generation of hydrogen peroxide, and NO and NO-derived species generated after production of NO caused further damage of various proteins in mitochondria, such as complexes I and II of the respiratory chain and pyruvate dehydrogenase (PDH). These results suggested that NO generated on reperfusion was the primary cause of mitochondrial dysfunction by damage of complexes I and II of the respiratory chain, with consequent increase of CF in the heart.     

Metabolic disarrangement in ischemic heart disease and its therapeutic control

The term myocardial ischaemia describes a condition which exists when fractional uptake of oxygen in the heart is not sufficient to maintain the rate of cellular oxidation. This leads to extremely complex situations which have been extensively studied in recent years. A large amount of experimental research has been directed to establish the precise sequence of biochemical events leading to myocyte necrosis as such knowledge could lead to rational treatments designed to delay myocardial cell death. At the present time there is no simple answer to the question of what determines cell death and no recovery on reperfusion. Problems arise because: (1) ischaemic damage is not homogeneous and many factors may combine to cause cell death; (2) severity of biochemical changes and development of necrosis are usually associated (both processes being dependent on the duration of the ischaemia) and it is impossible to establish a causal relationship; (3) the inevitability of necrosis can only be assessed by reperfusion of the ischaemic myocardium. Restoration of flow, however, might result in numerous further negative consequences, thus directly influencing the degree of recovery. From the clinical point of view, I have recently learned that there are several potential manifestations and outcomes associated with myocardial ischaemia and reperfusion. Without doubt ventricular dysfunction (either systolic or diastolic) of the ischaemic zone is the most reliable clinical sign of ischaemia, since ECG changes and symptoms are often absent. The ischaemia-induced ventricular dysfunction, at least initially, is reversible, as early reperfusion of the myocardium results in restoration of normal metabolism and contraction. In the ischaemic zone, recovery of contraction might occur instantaneously or, more frequently, with a considerable delay, thus yielding the condition recently recognized as the stunned myocardium. On the other hand, when ischaemia is severe and prolonged, cell death might occur. Reperfusion at this stage is associated with the release of intracellular enzymes, disruption of cell membranes, influx of calcium, persistent reduction of contractility, and eventual necrosis of at least a portion of the tissue. This entity has been called reperfusion damage by those who believe that much of the injury is the consequence of events occurring at the moment of reperfusion rather than as result of changes occurring during the period of ischaemia. The existence of reperfusion damage, however, has been questioned, and it has been argued that, with the exception of the induction of arrhythmias, it is difficult to be certain that reperfusion causes further injury. The existence of such an entity has clinical relevance, as it would imply the possibility of improving recovery with specific interventions applied at the time of reperfusion. In 1985 Rahimtoola described another possible out-come of myocardial ischaemia. He demonstrated that late reperfusion (after months or even years) of an ischaemic area showing ventricular wall-motion abnormalities might restore normal metabolism and function. He was the first to introduce the term hibernating myocardium, referring to ischaemic myocardium in which the myocytes remain viable but in which contraction is chronically depressed. Our data on metabolic changes occurring during ischaemia followed by reperfusion obtained either in the isolated and perfused rabbit hearts or in CAD patients undergoing intracoronary thrombolysis or aortocoronary by-pass grafting will be reviewed.     

Hoe 694, a new Na+/H+ exchange inhibitor and its effects in cardiac ischaemia

1. The benzoylguanidine derivative Hoe 694 ((3-methylsulphonyl-4- piperidino-benzoyl) guanidine methanesulphonate) was characterized as an inhibitor of Na+/H+ exchange in rabbit erythrocytes, rat platelets and bovine endothelial cells. The potency of the compound was slightly lower or comparable to ethylisopropyl amiloride (EIPA). 2. To investigate a possible cardioprotective role of the Na+/H+ exchange inhibitor Hoe 694, rat isolated working hearts were subjected to ischaemia and reperfusion. In these experiments all untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 10(-7) M Hoe 694 to the perfusate almost abolished reperfusion arrhythmias in the rat isolated working hearts. 3. Hoe 694 reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), which are indicators of cellular damage during ischaemia, into the venous effluent of the hearts by 60% and 54%, respectively. 4. The tissue content of glycogen at the end of the experiments was increased by 60% and the high energy phosphates ATP and creatine phosphate were increased by 240% and 270% respectively in the treated hearts as compared to control hearts. 5. Antiischaemic effects of the Na+/H+ exchange inhibitor, Hoe 694, were investigated in a second experiment in anaesthetized rats undergoing coronary artery ligation. In these animals, pretreatment with Hoe 694 caused a dose-dependent reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation down to doses of 0.1 mg kg-1, i.v. Blood pressure and heart rate remained unchanged. 6. We conclude that the new Na+/H+ exchange inhibitor, Hoe 694, shows cardioprotective and antiarrhythmic effects in ischaemia and reperfusion in rat isolated hearts and in anaesthetized rats. In view of the role which Na+/H+ exchange seems to play in the pathophysiology of cardiac ischaemia these effects could probably be attributed to Na+/H+ exchange inhibition.     

Myocardial protection after monophosphoryl lipid A: studies of delayed anti-ischaemic properties in rabbit heart

1. Monophosphoryl lipid A (MLA) is a non-pyrogenic derivative of Salmonella lipopolysaccharide. Administration of this agent at high doses to rats and at low doses to dogs was previously shown to confer marked protection against ischaemia-reperfusion 24 h later, although the cellular mechanisms of this delayed protection are obscure. We hypothesized that MLA pretreatment causes the induction of the 70 kDa cytoprotective stress protein HSP70i in the myocardium. If this were the case, protection against ischaemia-reperfusion injury would be observed both in vitro and in vivo. 2. Rabbits were pretreated with MLA 0.035 mg kg-1, i.v. or vehicle solution. For the in vitro study, hearts were isolated 24 h later and Langendorff-perfused with Krebs-Henseleit buffer at 37 degrees C. Global ischaemia was induced for 20 min followed by 120 min reperfusion. Recovery of post-ischaemic left ventricular function and lactate dehydrogenase efflux was similar in MLA and vehicle pretreated hearts and there was no significant difference in the percentage of infarction of the left ventricle determined by triphenyltetrazolium staining (MLA 22.4 +/- 5.2%, vehicle 24.8 +/- 5.1%). 3. When 30 min regional ischaemia and 120 min reperfusion was instituted in pentobarbitone-anaesthetized rabbits 24 h after pretreatment with MLA or vehicle, the percentage infarction within the risk zone was reduced from 42.6 +/- 5.7% in vehicle pretreated animals to 19.6 +/- 4.4% in MLA pretreated animals (P < 0.01). 4. Determination of myocardial HSP70i content by Western blot analysis showed that MLA treatment did not increase HSP70i immunoreactivity. 5. We conclude that MLA at this dose confers protection only against ischaemia-reperfusion injury in vivo and that this protection is not related to induction of HSP70i. Because protection was observed only in vivo it seems possible that the delayed protection conferred by MLA is mediated by effects on humoral or blood-borne factors.     

The electrocardiogram during physical stress and Holter monitoring in the detection of asymptomatic myocardial infarct

INTRODUCTION: In patients with myocardial infarction acute myocardial ischaemia could be manifested by characteristic ischaemic symptoms or noncharacteristic symptoms such as cardiac insufficiency or heart rhythm disturbances. Sometimes myocardial ischaemia is not followed by any symptom. This condition is known as asymptomatic myocardial ischaemia. Asymptomatic myocardial ischaemia usually could be detected by treadmill exercise tolerance test or 24-hour Holter ECG monitoring. PATIENTS AND METHODS: We analyzed a group of 58 patients suffering from myocardial infarction with ST segment depression during the treadmill exercise tolerance test. All patients were on Holter 24-hour ECG monitoring. As a criterion of myocardial ischaemia during Holter monitoring ST segment depression of 1 mm and more, lasting 1 minute and more, and 0.08" of J point was accepted. RESULTS: During the treadmill exercise tolerance test segment depression was not followed by any symptom in 18 (31%) patients. There were no differences in the number of patients with hypertension in the group with symptoms and the group without symptoms. Diabetes mellitus was more frequent in the group with asymptomatic myocardial ischaemia. The average values of maximum ST segment depression and heart rates during treadmill tests were not statistically significant in both groups (with and without symptoms). During daily activities myocardial ischaemia was found in 30 (51%) patients by a 24-hour Holter ECG monitoring. We observed 198 episodes of myocardial ischaemia of which 138 (69.1%) were asymtomatic. The amplitude of ST segment depression and duration of these changes were significantly greater in the group with symptomatic episodes than in the group with asymptomatic episodes of myocardial ischaemia. DISCUSSION: Asymptomatic myocardial ischaemia is an often appearance in patients with myocardial ischaemia. Almost in 25% of persons in whom sudden death occurred obstructive changes in coronary arteries during the autopsy were found. Asymptomatic myocardial ischaemia could be found even an a "completely healthy person" without any complaints. Asymptomatic myocardial ischaemia is usually detected in a "completely healthy person" by casual diagnosis, in patients with stable and non stable angina pectoris, in patients with stenosis of the coronary arteries proved by angiography, and in patients after myocardial infarction. Some authors considered that treadmill exercise tolerance testing is less reliable to discover asymptomatic myocardial ischaemia comparing to the continuous 24-hour Holter ECG monitoring. It is know that in patients with diabetes mellitus neuropathy precedes the onset of symptomatic myocardial ischaemia. Asymptomatic myocardial ischaemia has the same predictive value for prognosis of the disease as symptomatic myocardial ischaemia. In some patients "anginal alarm system" is defective, and perception and conduction of pain sensations are disturbed. CONCLUSION: 1. In 31% of patients who suffered from myocardial infarction with ST segment depression during the treadmill testing asymptomatic myocardial ischaemia was found. 2. By Holter monitoring ischaemia ST segment depression during the exertion is observed in 52% of patients. Most of ischaemic episodes were asymptomatic. 3. The amplitude of ST segment depression is significantly greater and duration of depression is significantly longer in symptomatic episodes of myocardial ischaemia comparing to asymptomatic myocardial ischaemia obtained by Holter ECG monitoring.     

Thrombolytic therapy does not change the release ratios of enzymatic and non-enzymatic myocardial marker proteins

Measurements of cardiac marker proteins in plasma from patients with acute myocardial infarction (AMI) have become important in the evaluation of recanalization therapy. The validity of this approach has however been questioned, because it was claimed that coronary reperfusion may increase the recovery in plasma of cardiac enzymes, such as creatine kinase (CK). In the present study, possible effects of thrombolytic therapy on the release of enzymatic and nonenzymatic marker proteins were investigated. Activities of CK and lactate dehydrogenase (LDH), and concentrations of myoglobin (Mb) and fatty acid-binding protein (FABP) were determined in serial plasma samples obtained from 50 patients with confirmed AMI, of whom 36 received thrombolytic therapy, and 14 did not. Treatment delay was 2.8+/-1.6 (mean+/-SD) h, and hospital delay in untreated patients was 2.7+/-1.8 h. Average infarct size, expressed in gram-equivalents of heart muscle per litre of plasma (g-eq/l), varied between 5.5 and 7.2 g-eq/l for the four marker proteins in patients treated with thrombolytic therapy, and between 4.6 and 6.4 g-eq/l in untreated patients, with a tendency to larger infarct sizes for Mb and FABP than for CK and LDH. Thrombolytic therapy, although significantly accelerating protein release rates, did not influence the release ratios. These results indicate that thrombolytic therapy has no significant effects on the recovery of cardiac marker proteins in plasma.     

Myoglobin concentration in serum as an early marker of reperfusion in patients with acute myocardial infarction after thrombolytic therapy

Detection of coronary artery reperfusion in patients after thrombolytic therapy because of acute myocardial infarction includes, except angiography, disappearance of anginal pain, regression of electrocardiographic and echocardiographic myocardial ischaemia symptoms, increased activity of creatine kinase (CPK) and its isoenzyme CK-MB. The aim of the study was to check whether changes in myoglobin serum concentration could be an early marker of coronary artery reperfusion after thrombolysis in patients with acute myocardial infarction. The studies comprised 50 patients treated by thrombolysis due to threatening myocardial infarction, including 29 men and 21 women aged 43-84 years. The patients were divided into 2 groups: the first (i)-patients without symptoms of coronary artery reperfusion and the second (ii)-those with symptoms of coronary artery reperfusion. It was assumed that the basis for successful reperfusion would be the reduction of total elevations of the ST segment 70% or more in electrocardiographic recording performed 3 hours after the start of thrombolytic treatment. Reperfusion was considered completely unsuccessful when reduction of total elevations was less than 30%. In patients with reperfusion after thrombolysis the concentrations of myoglobin were much higher and the activity of CPK and CK-MB significantly more intensive in comparison with patients without reperfusion symptoms in electrocardiographic assay. The evaluation of myoglobin concentration, CPK and CK-MB activity in the 3rd hour after the start of thrombolytic treatment in relation to maximum values is characterised by high sensitivity and specificity in the prediction of reperfusion onset Maximum myoglobin concentration in serum appears significantly earlier than maximum CPK and CK-MB activity and this marker is characterised by higher sensitivity and specificity in the evaluation of coronary artery reperfusion than the activity of CPK and CK-MB.     

Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice

Generation of free radicals upon reperfusion has been cited as one of the major causes of ischaemia/reperfusion injury. The following series of experiments was designed to study the effect of manganese superoxide dismutase (MnSOD) overexpression in transgenic mice on ischemia/reperfusion injury. A species of 1.4 kb human MnSOD mRNA was expressed, and a 325% increase in MnSOD activity was detected in the hearts of transgenic mice with no changes in the other antioxidant enzymes or heat shock proteins. Immunocytochemical study indicated an increased labeling of MnSOD mainly in the heart mitochondria of the transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed as heart rate x left ventricular developed pressure, was 52 +/- 4% in the transgenic hearts as compared to 31 +/- 4% in the non-transgenic hearts. This protection was accompanied by a significant decrease in lactate dehydrogenase release from the transgenic hearts. Overexpression of MnSOD limited the infarct size in vivo in a left coronary artery ligation model. Our results demonstrate that overexpression of MnSOD renders the heart more resistant to ischemia/reperfusion injury.     

Double blind randomised controlled trial of effect of metoprolol on myocardial ischaemia during endoscopic cholangiopancreatography

OBJECTIVE: To evaluate the effect of metoprolol, a beta adrenergic blocking drug, on the occurrence of myocardial ischaemia during endoscopic cholangiopancreatography. DESIGN: Double blind, randomised, controlled trial. SETTING: University Hospital. SUBJECTS: 38 (two groups of 19) patients scheduled for endoscopic cholangiopancreatography. INTERVENTIONS: Metoprolol 100 mg or placebo as premedication two hours before endoscopy. MAIN OUTCOME MEASURES: Heart rate, arterial oxygen saturation by continuous pulse oximetry, ST segment changes during endoscopic cholangiopancreatography (an ST segment deviation > 1 mV was defined as myocardial ischaemia), electrocardiogram monitored continuously with a Holter tape recorder. RESULTS: All patients had increased heart rate during endoscopy compared with rate before endoscopy, but heart rate during endoscopy was significantly lower in the metoprolol group compared with the placebo group (P = 0.0002). Twenty one patients (16 placebo, 5 metoprolol; P = 0.0008) developed tachycardia (heart rate > 100/min) during the procedure, and 11 patients (10 placebo, 1 metoprolol; P = 0.003) developed myocardial ischaemia. One patient in the placebo group had an acute inferolateral myocardial infarction. In the 10 other patients with signs of myocardial ischaemia during endoscopy the ST deviation disappeared when the endoscope was retracted. In all patients myocardial ischaemia was related to increases in heart rate, and 10 of the 11 patients had tachycardia coherent with myocardial ischaemia. CONCLUSIONS: Metoprolol prevented myocardial ischaemia during endoscopic cholangiopancreatography, probably through lowering the heart rate. Thus, tachycardia seems to be a key pathogenic factor in the development of myocardial ischaemia during endoscopy.     

Release of endothelin from the porcine heart after short term coronary artery occlusion

OBJECTIVE: Endothelin is increased in plasma following myocardial infarction. Whether brief periods of myocardial ischaemia not leading to myocardial infarction increase plasma endothelin is not known. Thus, the present study was designed to examine cardiac endothelin balance in association with a 10 min coronary artery occlusion followed by reperfusion. METHODS: Venous blood was selectively sampled from the transiently ischaemic myocardium using a shunt between the anterior interventricular vein and the right atrium in eight pentobarbitone anaesthetised pigs. Flow in the shunt was measured with a Doppler flow probe. Arterial blood was drawn from the aortic arch. Plasma endothelin was measured using an Endothelin 1-21 specific [125I] assay system. This assay system has no cross reactivity with big endothlin. RESULTS: A net cardiac endothelin uptake of 0.7(0.3-1.4) fmol.min-1 x g-1 (median, 95% confidence interval) in the control period shifted to a net release during the first 10 min of reperfusion. The release reached a maximum of 2.8(0.4-6.0) fmol.min-1 x g-1 after 1.5 min of reperfusion. Cardiac venous endothelin concentration increased from 3.4(2.5-4.8) to 4.4(3.6-6.9) and 4.4(3.6-6.6) fmol.ml-1 at 1.5 and 5 min of reperfusion, respectively (p < 0.001 for both). Arterial endothelin concentration decreased from 4.8(3.9-6.1) to 2.7(2.4-4.3) fmol.ml-1 at 10 min of reperfusion (p < 0.001). CONCLUSION: Endothelin is released from the heart for several minutes during reperfusion following a brief coronary artery occlusion.     

The prehospital phase of patients with suspected acute myocardial infarct: results of the Oltner Cardiac Emergency Study

Early reperfusion in acute myocardial infarction has been shown to reduce myocardial damage and to improve prognosis. The goals of this study, the Olten Cardiac Emergency Study, were to identify the factors, related to the patients or to the emergency medical services, which influenced pre-hospital delay in patients with symptoms suggestive of acute myocardial infarction. From November 1, 1992, to June 15, 1993, all the events occurring between symptom onset and hospital discharge where analyzed for 341 such patients who were cared for by the emergency networks connected with the Cantonal Hospital, Olten: in addition, follow-up at 3 months was obtained on all patients discharged alive. Of the 341 patients, 14 (4.1%) died out of the hospital. The final diagnoses of the 327 patients admitted to the emergency department were: acute myocardial infarction 18.3%; unstable angina 10.1%; stable angina 3.4%; non-ischemic cardiac diseases 29.4%; other non-cardiac diseases 38.8%. Mean delay between symptom onset and arrival at the hospital was 8 h 55 min (median delay 4 h 10 min); for patients with a final diagnosis of acute myocardial infarction, mean delay was 9 h 43 min (median delay 5 h 10 min). Patient delay was surprisingly long and represented 70.4% of the total pre-hospital delay; 56.6% of the patients did not realize that their symptoms were serious and only 47.1% (and 68.3% of the patients with acute myocardial infarction) came to the hospital by ambulance. These long pre-hospital delays were responsible for the low (13.3%) thrombolysis rate of patients with acute myocardial infarction. We conclude that pre-hospital delay was much too long in our population. Improvements can only be achieved through patient education and better efficiency of emergency networks. Our findings underline the need for public education campaigns on heart attacks.     

The protective reaction of the myocardium to ischemic damage

The morphological and functional consequences of epinephrine-induced myocardial infarction were studied in normo- (Wistar) and hypertensive (ISIAH) rats. After experimental myocardial infarction there was an irreversible transition to the "worn-out" stage or "plastic damage" to the myocardium. Thus, myocardial hibernation in ISIAH rats anticipates and determines the development of myocardial stunning, i.e., irreversible myocardial damage, whereas in the normotensive animals, the protective effect of hibernation is fully shown. The ontogenetic features of myocardial response of ISIAH rats to hypoxia promote transformation of adaptive hibernation and stunning to maladaptive pathological changes causing hypoxic alterations.