Myocardial potassium uptake and catecholamine release during cardiac sympathetic nerve stimulation

To determine whether sympathetic nerve stimulation induces a significant potassium uptake in the myocardium, the changes in myocardial potassium balance, catecholamine release, lactate uptake, and oxygen consumption were recorded in eight anaesthetised open chest pigs during electrical stimulation of the right intermediate cardiac nerve at 10 Hz. Potassium concentrations were continuously measured by polyvinylchloride valinomycin minielectrodes in arterial and coronary sinus blood. Potassium concentration in coronary sinus blood fell to a nadir 0.42(0.21-0.61) mmol.litre-1 below control values (median and 95% confidence interval) and resulted in a peak potassium uptake of 65(38-102) mumol.min-1 100 g-1 after 2.5(2.0-3.0) min, which correlated (r = 0.94, p less than 0.001) with cardiac noradrenaline release. Accumulated myocardial potassium uptake amounted to 139(82-241) mumol.100 g-1 when a stable potassium concentration difference between arterial and coronary sinus blood was reached after 5.5(4.25-6.50) min. Cardiac contractility (LV dP/dt), myocardial oxygen consumption, and lactate uptake rose from control to peak potassium uptake (p less than 0.001) by 140%, 158%, and 92% respectively. Coronary sinus blood noradrenaline and adrenaline concentrations rose significantly (p less than 0.01) from 58(44-87) pg.ml-1 at control to 2208(1159-5627) pg.ml-1 at peak uptake and from 15(11-19) pg.ml-1 to 85(64-230) pg.ml-1 respectively. Arterial noradrenaline increased from 29(19-41) pg.ml-1 to 374(176-640) pg.ml-1 and arterial adrenaline rose from 15(11-23) pg.ml-1 to 31(24-52) pg.ml-1 (p less than 0.001). It is concluded that sympathetic nerve stimulation induces a substantial myocardial potassium uptake in a dose dependent relation to cardiac noradrenaline release and alters the contractile and metabolic state of the heart substantially with only minor changes in arterial catecholamine concentration.     

Release of neuropeptide Y and noradrenaline from the human heart after aortic occlusion during coronary artery surgery

STUDY OBJECTIVE--The aim was to study the influence of complete myocardial ischaemia during aortic occlusion on release of neuropeptide Y and noradrenaline from the human myocardium. DESIGN--Coronary sinus neuropeptide Y and noradrenaline were measured after 46(SEM 7) min of aortic occlusion with cold cardioplegia in patients undergoing coronary artery surgery. Patients - Seven patients (all male), aged 64(SEM 3) years, were studied. All were undergoing coronary artery bypass grafting. MEASUREMENTS AND MAIN RESULTS--Reperfusion was associated with an increase in coronary sinus blood flow as determined by thermodilution. Simultaneously there was cardiac release of both neuropeptide Y and noradrenaline during the first two sampling periods: 3(0.6) and 7(0.6) min after the start of reperfusion. The outflow of neuropeptide Y and noradrenaline returned to preischaemic values by 14(1) min after reperfusion. Coronary sinus blood lactate and pyruvate concentrations were also increased at the start of reperfusion, while the lactate/pyruvate ratio remained unchanged. Myocardial oxygen uptake was not influenced by cardiac ischaemia. CONCLUSIONS--Ischaemia of the human heart in vivo is associated with an enhanced outflow of neuropeptide Y and noradrenaline from the heart. Since arterial blood concentrations of these substances were also increased on reperfusion, their release is probably due to increased sympathetic nerve activity, though other mechanisms such as temperature change and local metabolite formation could also participate. Local release of neuropeptide Y during cardiac ischaemia may be involved in the regulation of coronary vascular tone as well as in the release of noradrenaline and acetylcholine.     

Cardiac release of chemoattractants after ischaemia induced by coronary balloon angioplasty.

OBJECTIVE--To investigate the release of chemoattractants after myocardial ischaemia during balloon angioplasty. DESIGN--Sampling of femoral arterial and coronary sinus blood before and immediately after the first balloon inflation during angioplasty. In a study group of 16 patients the balloon was kept expanded for two minutes, whereas in a control group of eight patients the first balloon inflation was brief (< 10 s). MAIN OUTCOME MEASURES--Chemotaxis of neutrophils from healthy donors towards patient plasma (Boyden chamber), superoxide anion production by normal neutrophils after incubation with patient plasma (cytochrome C reduction). RESULTS--In the study group, coronary sinus plasma after balloon deflation was more chemoattractive to normal neutrophils (median relative increase 24% (quartiles: 4%, 45%), p = 0.008) and induced a higher superoxide anion production in normal neutrophils (44% (10%, 97%), p = 0.013) than arterial plasma. Concomitantly, the degree of activation of patient neutrophils was increased in coronary sinus blood compared with arterial blood, as shown by an increased proportion of neutrophils reducing nitro-blue tetrazolium (21% (9%, 38%), p = 0.006) and a decreased neutrophil filter-ability (-16%(-3%, -40%), p = 0.003) in coronary sinus blood. In the study group before balloon inflation and in the control group before and after balloon inflation differences between arterial and coronary sinus blood were not significant. Signs of ischaemia (lactate release, ST segment changes) were only detected in the study group. CONCLUSION--After transient myocardial ischaemia during balloon angioplasty there is a local release of chemoattractants, associated with neutrophil activation.     

Ventricular wall motion and NE release in post-ischemic reperfused myocardium

To clarify the relationship between post-ischemic myocardial dysfunction and local cardiac sympathetic nerve function, we measured regional myocardial length and norepinephrine (NE) release during sympathetic nerve stimulation in 32 mongrel dogs. Coronary occlusion was produced by balloon occluder for 15 min and reperfused for 60 min. Dogs were divided into 3 groups as follows; Group 1 (n = 14): Sympathetic nerve stimulation, Group 2 (n = 9): Pre-treatment with yohimbine hydrochloride (0.2 mg/kg) and sympathetic nerve stimulation, Group 3 (n = 9): Exogenous NE administration. Sympathetic nerve stimulation or NE infusion were performed before occlusion and after reperfusion. In group 1, the extent of the increase in systolic shortening during sympathetic nerve stimulation (delta - shortening) lowered at 5 min after reperfusion and augmented progressively. But, delta-shortening at an early reperfusion period did not reduce in group 2 and 3. NE release from the ischemic myocardium decreased in group 1 and did not recover for 60 min. When the cardiac sympathetic nerve was denervated with 90% phenol solution, NE release further decreased in group 1. On the other hand, NE release did not decrease in group 2. These results indicate that the response to sympathetic nerve stimulation decreased in post-ischemic reperfused myocardium and this was due to diminished NE release. It was considered that sympathetic nerve conduction was not completely impaired in post-ischemic myocardium and pre-synaptic alpha-2 receptor mediated negative feedback mechanism would play an important role in these diminished NE release.     

Effect of the carotid sinus nerve stimulation on nutritive myocardial blood flow in regional cardiac ischaemia

The authors have studied the local blood flow regulation of the heart under the influence of the stimulation of the carotid sinus nerve in segmental myocardial ischaemia. The experiments were carried out on 38 dogs. By ligating the mid-portion of the left anterior descending coronary artery, a small artificial infarction has been produced. Circulatory examinations were made after 24 hours following the coronary ligation. In 18 dogs the circulatory investigations were done during the electrical stimulation of the carotid sinus nerve while 20 dogs were used as control. The local nutritive blood flow of the heart was measured by the administration of 86 rubidium in the intact zone, in the ischaemia (necrotic) zone and at the border zone of the heart. According to the experimental data, under the influence of the carotid sinus nerve stimulation the blood flow of the intact zone does not change considerably while the necrotic and border zones increases to a great extent. Reflex redistribution of the myocardial blood flow probably plays a decisive role in the antianginal effect of carotid sinus nerve stimulation.     

Plasma-mediated stimulation of neutrophil superoxide anion production during coronary artery bypass grafting: role of endothelin-1.

BACKGROUND: Activation of polymorphonuclear neutrophils (PMN) and subsequent release of free oxygen radicals, including the superoxide anion (O2-) has been shown to result in postischaemic myocardial dysfunction during coronary artery bypass grafting (CABG). Several neutrophil-oriented stimuli are known to be released from myocardium during ischaemia and reperfusion. Release of endothelin-1 has been documented during CABG. The aim of the current study was to evaluate plasma-mediated neutrophil stimulation and to verify whether endothelin-1, known to be a stimulus for PMN, is involved in plasma-mediated stimulation of PMN during coronary artery bypass grafting. METHODS: Plasma samples from peripheral artery, peripheral vein, and coronary sinus were obtained from 21 patients undergoing CABG before aortic clamping (global ischaemia), immediately after beginning reperfusion, and 30 min after reperfusion as well as from healthy controls. Plasma was incubated with PMN isolated from healthy donors preincubated in the presence of saline or specific endothelin-1 receptor antagonist (ET-A). PMN O2- production was measured spectrophotometrically. RESULTS: Plasma samples taken from the coronary sinus at the beginning of reperfusion were capable of higher stimulation of neutrophil superoxide anion production (24.2 +/- 2.0 nmol/5 x 10(6)PMN/30 min) than plasma obtained before reperfusion (15.6 +/- 1.5; p < 0.05) or plasma taken from peripheral artery (17.1 +/- 1.7; p < 0.05). Preincubation of PMN with endothelin-1 receptor antagonist decreased superoxide anion production by cells exposed to plasma taken from coronary sinus at the beginning of reperfusion (17.6 +/- 2.0, p < 0.05). CONCLUSIONS: Transcardiac release of soluble stimuli for PMN occurs as a result of myocardial ischaemia during CABG. Endothelin-1 may be involved in the plasma-mediated stimulation of neutrophil superoxide anion production.     

Lipid peroxidation during myocardial ischaemia induced by pacing

Oxygen derived free radical generation can be shown in experimental models of myocardial ischaemia and reperfusion and may cause cellular damage by peroxidizing polyunsaturated membrane phospholipids. An attempt was made to quantify human intracardiac lipid peroxidation during transient myocardial ischaemia by measuring the aortic and coronary sinus concentrations of malondialdehyde (a marker of lipid peroxidation) before, during, and after incremental pacing. Twenty six patients were paced until they had severe chest pain or 2 mm ST segment depression or they reached a paced rate of 180 beats/min. They were divided into two groups according to whether or not lactate was produced during pacing. Twelve patients (group 1), all with coronary artery disease, produced myocardial lactate during pacing. None of the other 14 patients (group 2), half of whom had coronary disease, produced lactate during pacing. Concentrations of malondialdehyde in the aorta and coronary sinus were significantly higher in group 1 than in group 2. Five minutes after the end of pacing coronary sinus malondialdehyde concentrations in group 1 had increased significantly from baseline values. There were no changes with time in the coronary sinus concentration of malondialdehyde in group 2 or in the aorta in either group. The negative malondialdehyde extraction ratio in group 1 suggests that intracardiac lipid peroxidation occurs during transient human myocardial ischaemia.     

Lipid peroxidation during myocardial ischaemia induced by pacing.

Oxygen derived free radical generation can be shown in experimental models of myocardial ischaemia and reperfusion and may cause cellular damage by peroxidizing polyunsaturated membrane phospholipids. An attempt was made to quantify human intracardiac lipid peroxidation during transient myocardial ischaemia by measuring the aortic and coronary sinus concentrations of malondialdehyde (a marker of lipid peroxidation) before, during, and after incremental pacing. Twenty six patients were paced until they had severe chest pain or 2 mm ST segment depression or they reached a paced rate of 180 beats/min. They were divided into two groups according to whether or not lactate was produced during pacing. Twelve patients (group 1), all with coronary artery disease, produced myocardial lactate during pacing. None of the other 14 patients (group 2), half of whom had coronary disease, produced lactate during pacing. Concentrations of malondialdehyde in the aorta and coronary sinus were significantly higher in group 1 than in group 2. Five minutes after the end of pacing coronary sinus malondialdehyde concentrations in group 1 had increased significantly from baseline values. There were no changes with time in the coronary sinus concentration of malondialdehyde in group 2 or in the aorta in either group. The negative malondialdehyde extraction ratio in group 1 suggests that intracardiac lipid peroxidation occurs during transient human myocardial ischaemia.     

Quantitation of coronary venous adenosine in patients: limitations evaluated by radioimmunoassay

Experimental studies have shown that adenosine is rapidly released in response to myocardial ischaemia. To evaluate whether coronary venous adenosine release is a metabolic characteristic of myocardial ischaemia in patients, adenosine concentrations were measured by a highly sensitive and specific radioimmunoassay. In three patients with normal coronary arteries and in seven with obstructive coronary artery disease coronary venous adenosine content was measured at rest and during atrial pacing. When whole blood or plasma were extracted immediately with perchloric acid the adenosine content was found to be lower than that previously reported. Recovery studies showed that the importance of time and temperature at low adenosine concentrations had been underestimated in preceding studies. In patients with coronary artery disease coronary venous adenosine concentration increased from 106.3(48.8) nmol.litre-1 to 114.9(57.0) nmol.litre-1 (NS) during pacing and was 130.4(63.3) nmol.litre-1 (NS) 2 min after pacing. Even in the presence of lactate production enhanced adenosine release was not consistently evidenced. Furthermore, venous adenosine content did not increase in five patients undergoing coronary artery occlusion during angioplasty of the left anterior descending coronary artery. The extremely short half life of coronary venous adenosine appears to preclude its use as an index of myocardial ischaemia in patients.     

Inhibition of adrenergic neurotransmission in ischaemic regions of the canine left ventricle

To test hypothesis that adrenergic neurotransmission is impaired in acute myocardial ischaemia, we studied contractile function of normal and ischaemic myocardium after coronary artery occlusion. For each area we compared the contractile response to left sympathetic nerve stimulation (LSS) with the response to exogenous noradrenaline (NA). Contractile response was measured with intramyocardial sonomicrometers. LSS increased aortic pressure and heart rate. NA was infused to achieve an aortic pressure equivalent to LSS and simultaneous atrial pacing matched the heart rate during LSS. In normal zones both interventions produced increased shortening equivalently. In ischaemic zones systolic expansion was unchanged during LSS, while NA improved contractile function of the same zones by decreasing systolic expansion. These responses occurred during ischaemia produced by either anterior or posterior descending coronary occlusion. Changes in regional blood flow, measured by 8 microns radiolabelled microspheres, could not account for the difference between the ischaemic regional response to LSS or NA. We conclude that acute regional ischaemia impairs adrenergic nerve transmission.     

Lack of platelet-activating factor release during reversible myocardial ischaemia.

Platelet-activating factor (PAF) is involved in experimental models of myocardial ischaemia, and PAF infusion can cause thromboxane release. Thromboxane is produced during brief episodes of reversible myocardial ischaemia in patients with coronary heart disease. To learn whether PAF synthesis is associated with thromboxane production in mild myocardial ischaemia, we performed rapid atrial pacing in four patients with angina pectoris which caused chest pain, ST segment depression (delta ST = -1.8 +/- 0.2 mm) and lactate excretion in the coronary sinus (percent lactate extraction decreased from 20 +/- 6% to -15 +/- 9%). Thromboxane B2 was produced causing a positive transmyocardial gradient (from 88 +/- 154 pg.ml-1 baseline to 1770 +/- 1407 pg.ml-1 at the peak) but there was no PAF release into coronary sinus blood. In four other patients we determined whether more pronounced ischaemia could be associated with PAF synthesis. Coronary sinus blood was sampled before and during balloon occlusion of a major coronary artery: PAF was not detected in coronary sinus, whereas percent lactate extraction decreased from 24 +/- 6% to -63 +/- 22% (n = 4). We conclude that PAF plays a minor role in short episodes of reversible ischaemia and does not participate in thromboxane production.     

Beta endorphin release in patients after spontaneous and provoked acute myocardial ischaemia.

BACKGROUND--In animal models of circulatory shock and heart failure concentrations of the endogenous opioid peptide beta endorphin are raised and opioid receptor blockade improves haemodynamic variables and survival. This study was performed to identify whether acute myocardial ischaemia provokes the release of beta endorphin in humans. METHODS--Observational study in a university cardiology centre. Serial measurements of beta endorphin made by specific radioimmunoassay were correlated with other clinical and neuroendocrine variables that were measured prospectively. Fifty five patients with acute myocardial ischaemia and 26 patients undergoing elective coronary angioplasty of the left anterior descending coronary artery were studied. RESULTS--beta endorphin concentrations were raised above the upper limit of normal in 31/42 (74%) patients with confirmed myocardial infarction, 3/13 (23%) patients with unstable angina, and 10/24 (42%) patients after coronary angioplasty. There was no evidence of myocardial release of beta endorphin. There were significant positive correlations between beta endorphin and the concentrations of adrenocorticotrophic hormone, cortisol, and arginine vasopressin. In patients with acute myocardial ischaemia there was a significant positive correlation between the peak concentrations of creatine kinase and beta endorphin but no correlation with visual analogue scores of the intensity of chest pain. The highest beta endorphin concentrations were seen in patients whose clinical course was complicated by the development of heart failure. CONCLUSIONS--beta endorphin release is a component of the neuroendocrine activation associated with myocardial ischaemia/infarction.     

Beta endorphin release in patients after spontaneous and provoked acute myocardial ischaemia.

BACKGROUND--In animal models of circulatory shock and heart failure concentrations of the endogenous opioid peptide beta endorphin are raised and opioid receptor blockade improves haemodynamic variables and survival. This study was performed to identify whether acute myocardial ischaemia provokes the release of beta endorphin in humans. METHODS--Observational study in a university cardiology centre. Serial measurements of beta endorphin made by specific radioimmunoassay were correlated with other clinical and neuroendocrine variables that were measured prospectively. Fifty five patients with acute myocardial ischaemia and 26 patients undergoing elective coronary angioplasty of the left anterior descending coronary artery were studied. RESULTS--beta endorphin concentrations were raised above the upper limit of normal in 31/42 (74%) patients with confirmed myocardial infarction, 3/13 (23%) patients with unstable angina, and 10/24 (42%) patients after coronary angioplasty. There was no evidence of myocardial release of beta endorphin. There were significant positive correlations between beta endorphin and the concentrations of adrenocorticotrophic hormone, cortisol, and arginine vasopressin. In patients with acute myocardial ischaemia there was a significant positive correlation between the peak concentrations of creatine kinase and beta endorphin but no correlation with visual analogue scores of the intensity of chest pain. The highest beta endorphin concentrations were seen in patients whose clinical course was complicated by the development of heart failure. CONCLUSIONS--beta endorphin release is a component of the neuroendocrine activation associated with myocardial ischaemia/infarction.     

Plasma mediated neutrophil stimulation during coronary angioplasty: autocrine effect of platelet activating factor.

BACKGROUND--Polymorphonuclear neutrophils are involved in the development of myocardial injury during ischaemia and reperfusion. Coronary angioplasty has been shown to result in neutrophil activation. This may be a result of contact with ligands expressed by endothelial cells or response to soluble stimuli released from ischaemic tissue into the plasma or both. OBJECTIVE--To investigate plasma mediated neutrophil activation during angioplasty. METHODS AND RESULTS--Plasma samples were collected from the coronary sinus, femoral artery, and femoral vein of 14 patients undergoing angioplasty, before and after the first balloon inflation and at the end of the procedure. Plasma samples were incubated with washed neutrophils isolated from healthy donors. Expression of the adhesion molecules CD18 integrin and L-selectin (Leu-8) was measured by flow cytometry, and superoxide anion production was measured by chemiluminescence. Plasma samples from the coronary sinus and femoral artery but not from the peripheral vein induced increased expression of neutrophil CD18 after balloon deflation. Modification of the expression of L-selectin was not noted. Production of superoxide anion by neutrophils was stimulated by plasma samples from the coronary sinus, but not by those from the femoral artery or vein. This plasma mediated neutrophil stimulation was prevented when the neutrophils were pretreated with platelet activating factor receptor antagonists BN52021 or BN50739. The platelet activating factor concentration detected in the coronary sinus was not higher than in control plasma. CONCLUSION--Brief ischaemia during coronary angioplasty leads to the release of soluble stimuli capable of inducing neutrophil integrin expression and free oxygen radical production. Platelet activating factor may act as an autocrine neutrophil stimulus under these conditions.     

Intracoronary enalaprilat during angioplasty for acute myocardial infarction: alleviation of postischaemic neurohumoral and inflammatory stress?

AIM: Reperfusion after myocardial ischaemia is associated with a distinct ischaemia/reperfusion injury. Since ACE-inhibition, beyond its influence on cardiac angiotensin II formation and kinin metabolism, has been shown to be cardioprotective by decreasing leucocyte adhesion and endothelin-1 (ET-1) release, we investigated the effects of intracoronary (i.c.) enalaprilat during primary angioplasty in acute myocardial infarction. METHODS AND RESULTS: Twenty-two patients were randomized to receive i.c. enalaprilat (50 micro g) or placebo immediately after reopening of the infarct-related artery (IRA). Plasma concentrations of soluble L-selectin, P-selectin, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), ET-1 and nitric oxide metabolite concentrations (NOx) were measured in pulmonary arterial blood. Coronary blood flow was assessed using corrected thrombolysis in myocardial infarction (TIMI) frame counts (CTFC). During reperfusion, there was a significant increase in sL-selectin, sP-selectin and ET-1 in the placebo group, which was greatly diminished by enalaprilat. Levels of sVCAM-1 and sICAM-1 were not affected in either group. CTFC in the placebo group remained higher than normal in both the IRA and nonculprit vessels, whereas myocardial blood flow improved with enalaprilat. CONCLUSION: Enalaprilat as adjunct to primary angioplasty might be a protective approach to prevent leucocyte adhesion and the release of ET-1, thereby improving coronary blood flow.     

Catecholamine release in coronary sinus during vasospastic angina induced by ergonovine

In seven patients with spontaneous angina and three control subjects, aortic and coronary sinus norepinephrine and epinephrine were assessed. Samples were taken in basal conditions and during ergonovine test in coronary sinus and aorta. The behaviour of some hemodynamic parameters as heart rate, blood pressure, left ventricular end diastolic pressure and coronary sinus flow was also studied. Resting myocardial norepinephrine and epinephrine flux was similar for both groups. In ischemic patients ergonovine induced a coronary spasm accompanied by an evident reduction of coronary sinus flow and a slight increase in arterial epinephrine and norepinephrine concentrations. However, a significant decrease in the net myocardial norepinephrine and epinephrine release was evidenced. After ergonovine, not significant changes in norepinephrine and epinephrine concentration and release resulted in control subjects. The increase in peripheral catecholamine concentrations found in ischemic patients during ergonovine test could represent a reflex activation of sympathetic activity induced by an ischemia dependent ventricular mechanical disfunction. The decrease in myocardial catecholamine release during angina could be justified by sequestration of epinephrine and norepinephrine in ischemic areas induced by vasospasm or reflex inhibition of cardiac sympathetic tone.     

Influence of residual myocardial ischaemia on induced ventricular arrhythmias following a first acute myocardial infarction.

OBJECTIVES: The purpose of this study was to assess the possible effect of residual myocardial ischaemia on induced ventricular arrhythmia during programmed ventricular stimulation in survivors of a first acute myocardial infarction. BACKGROUND: Most deaths after hospital discharge for acute myocardial infarction are sudden and presumably arrhythmic. Sudden cardiac death results from a dynamic interaction of structural abnormalities and transient triggering factors. The role of myocardial ischaemia as a trigger for ventricular arrhythmias remains unclear. We hypothesized that residual myocardial ischaemia after a first acute myocardial infarction is a potent trigger for sustained ventricular tachyarrhythmias, particularly in the presence of an abnormal myocardium. METHODS AND RESULTS: In this prospective study, programmed electrical stimulation, coronary angiography and dipyridamole-thallium-201 scintigraphy single-photon emission computed tomography were performed in 90 consecutive survivors of a first acute myocardial infarction. Patients, divided in two groups - group 1 with induced ventricular tachyarrhythmia (n=24) and group 2 without induced ventricular tachyarrhythmia (n=66) - were compared regarding residual myocardial ischaemia. The two groups were comparable in terms of mean left ventricular ejection fraction, infarct size and location, gender ratio, peak creatine kinase value, and extent of coronary disease. Residual myocardial ischaemia was detected in 32 patients: 15 (42.5%) belonged to group 1 and 17 (25.7%) to group 2. There was a statistically significant difference between the two groups regarding the presence and the extent of residual myocardial ischaemia (P<0.05). CONCLUSION: Residual myocardial ischaemia, revealed by dipyridamole-thallium-201 scintigraphy following a first acute myocardial infarction, might contribute to electrical instability evaluated by programmed ventricular stimulation.     

Cardiac Release and Kinetics of Endothelin After Uncomplicated Percutaneous Transluminal Coronary Angioplasty

This study was designed to assess the release kinetics of endothelin after percutaneous transluminal coronary angioplasty (PTCA) and to prove the coronary endothelium as the source of the endothelin release. Twenty-seven patients with single-vessel coronary artery disease underwent PTCA. Endothelin, troponin T, myoglobin, and creatine phosphokinase paired blood samples were withdrawn from the coronary sinus and a peripheral vein before the balloon maneuver and at 1, 5, 10, 30, 45 minute(s), and at 1, 2, 3, 6, 12, and 24 hour(s) after the last balloon maneuver. Myocardial ischemia was monitored by means of cardiac lactate metabolism and 12-lead electrocardiogram. Thirteen patients who underwent a diagnostic cardiac catheterization served as a control group. In the left coronary artery, PTCA (n = 19) endothelin concentrations increased from 4.1 pg/ml as a common mean baseline level before intervention to 13.9 ± 2.6 pg/ml (mean ± SD) in the coronary sinus and 7.9 ± 2.2 pg/ml (mean ± SD) in the peripheral vein at 1 minute after the intervention (p <0.001). The levels remained elevated for 3 hours with higher coronary sinus than peripheral venous concentrations due to persistant cardiac endothelin release. PTCA of the right coronary artery (n = 8) also led to an instantaneous endothelin increase from a mean concentration of 4.4 before intervention to 8.3 pg/ml after intervention with identical coronary sinus and peripheral venous levels (p <0.001). Endothelin levels gradually decreased to normal within 6 hours. No patient developed a measurable myocardial ischemia or a myocardial infarction. In the control group all parameters remained unchanged. Uncomplicated PTCA was followed by a significant cardiac endothelin release that seems to indicate endothelial injury and not myocardial ischemia.     

Myocardial contractility evaluated from cross-oriented segments during {beta}-adrenergic blockade or sympathetic nerve stimulation

In patient and experimental models of regions of the left ventriclesubjected to ischaemia and thus made dysfunctional it is importantto characterize the inotropic state of the remaining myocardium.Eighteen pentobarbitone-anaesthetized open-chest cats with anacute circumflex coronary artery occlusion were therefore studiedduring either sympathetic nerve stimulation (n=9), or afterß-adrenergic blockade (n=9). Myocardial contractilitywas evaluated from cross-oriented segments in the left ventricularanterior wall during stable haemodynamics and during 5 s inferiorcaval occlusion. The end-systolic pressure-length relationshipof longitudinal segments was rather insensitive to ß-adrenergicblockade and sympathetic nerve stimulation. The end-systolicpressure-length relationship of circumferential segments wassuitable as a marker of contractility in the low contractilityrange, whereas the peak systolic shortening velocity parameterwas more suitable in the upper contractility range. The pressure-lengthloop area versus end-diastolic length relationship of both circumferentialand longitudinal segments reflected both increased and decreasedleft ventricular inotropic state. We therefore conclude thatthe pressure-length loop area versus end-diastolic length relationshipis the best index of regional myocardial contractility in regionalischaemic hearts.     

Endothelin-1 in patients with coronary heart disease undergoing cardiac catheterization

Objectives. This study examined the possible association between endothelin and coronary atherosclerosis and evaluated the synthesis and release of endothelin in the presence of various stimuli that occur during cardiac catheterization.Background. Circulating endothelin has been reported to be increased in diffuse atherosclerosis and acute myocardial infarction. However, the relation between coronary artery disease and endothelin release remains unclear.Methods. We measured the plasma and urinary concentrations of endothelin immunoreactivity in 45 patients and 10 healthy control subjects.Results. In group IA (n = 9), simultaneous blood sampling in the coronary sinus and femoral artery during coronary angioplasty of the left anterior descending coronary artery demonstrated no immediate changes in plasma immunoreactive endothelin-1 (ir-ET-1) levels. In 11 patients in group IB undergoing coronary angioplasty of a major artery, we did not detect changes in peripheral plasma concentrations of ir-ET-1 within 24 h, but urinary ir-ET-1 levels increased from 9.2 ± 2.3 to 18.6 ± 4.9 pg/mg of creatinine a few hours after coronary angioplasty (mean ± SEM, p < 0.05). This increase in urinary endothelin excretion persisted 24 h later. Group II patients (n = 12) had coronary angiography without coronary angioplasty. Levels of both plasma and urinary ir-ET-1 did not change during the 24-h follow-up period. There was no relation between the severity of coronary atherosclerosis and the plasma or urinary concentrations of ir-ET-1. Systolic aortic pressure correlated with basal urinary excretion of endothelin (r = 0.54, p = 0.03, n = 15). In group III (n = 13), levels of ir-ET-1 in patients undergoing right heart catheterization without angiography did not differ from those in the control group.Conclusions. The presence or the severity, or both, of coronary atherosclerosis is not associated with a detectable increase in endothelin release. The diagnostic procedures of Catheterization do not modify endothelin concentrations in plasma and urine. Vascular stretch or injury, or both, during coronary angioplasty increases urinary ir-ET-1 levels a few hours after the procedure. This increase persists for at least 24 h but is not detectable by brief sampling of peripheral or coronary sinus blood.