Management Of Myocardial Ischemia Research Articles

Plasma endothelin-1 levels during transient acute myocardial ischaemia in men: effects of coronary revascularization.

The endothelium-derived peptide endothelin-1 (ET-1) was evaluated in 14 male patients [mean age 52.74 years (SEM 1.10)] affected by coronary artery disease during a bicycle electrocardiographic stress test and dipyridamole echocardiogram. Both tests were performed before and after coronary revascularization. Fourteen healthy male subjects served as controls [mean age 53.21 years (SEM 1.63)]. Baseline plasma endothelin-1 levels were higher (P < 0.0001) in ischaemic patients [1.81 pg mL-1 (0.15, n = 14)] than in control subjects [0.61 pg mL-1 (0.03, n = 14)], but did not increase with exercise in both groups. Similar results were obtained with dipyridamole infusion. Endothelin-1 levels significantly decreased after coronary revascularization [before: mean 1.81 pg mL-1 (SEM 0.15, n = 14); after: mean 1.16 pg mL-1 (SEM 0.11), P < 0.002], without changes in the peptide response to both tests. In conclusion, elevated plasma endothelin-1 concentrations were found in patients with stable angina compared with non-ischaemic subjects. No changes were observed during exercise or dipyridamole infusion in both groups. Coronary revascularization was followed by a significant decrease in plasma endothelin-1 levels.

Endothelium, coronary vasodilation, and organic nitrates

Recent investigations have suggested that the vascular endothelium is an active participant in the regulation of arterial tone and blood flow. In a state of health, the endothelium contributes to hemodynamic equilibrium; however, it rapidly becomes dysfunctional in hypercholesterolemia and diabetes mellitus or with exposure to the stress of hypertension or long-term smoking. Among the deficits observed during endothelial dysfunction is a reduction in the synthesis and release or an excessive degradation of EDRF. This potent vasorelaxant is derived from the amino acid l-arginine and has been characterized as NO or a closely related substance. EDRF relaxes vascular smooth muscle by activating guanylate cyclase. A deficiency in the activity of EDRF may be the mechanism of diminished coronary vasodilation in patients with ischemic heart disease. Organic nitrates, which are metabolized to NO or S-nitrosothiol at the cellular level, are often used in the management of myocardial ischemia; they also induce vasodilation by activating guanylate cyclase. The similarities between organic nitrates and endogenous EDRF and their interactions are discussed in this review.

Characteristics and clinical significance of ambulatory myocardial ischemia in men and women in the general population presenting with angina pectoris

Objectives. The aim of this study was to determine the frequency and prognostic importance of ambulatory myocardial ischemia and its association with cardiovascular risk factors in men and women in the general population presenting for the first time with typical angina pectoris.Background. Previous studies in selected “low” and “high” risk patients with stable coronary heart disease report a wide range in the frequency of ischemia (24% to 82%) and there is no agreement about whether ambulatory ischemia is of prognostic importance for the generality of patients with stable angina.Methods. Consecutive patients ≤70 years of age from a randomly selected population with no previous coronary heart disease were assessed prospectively, and 96 patients with typical angina and 95 age-, gender- and practice-matched asymptomatic control subjects underwent 24-h ambulatory ST segment monitoring before antianginal therapy. All recordings were analyzed in blinded fashion. Follow-up evaluation of patients with angina to assess for revascularization, myocardial infarction and death was undertaken at a mean of 15.8 months (range 7 to 30) after the initial evaluation.Results. Transient episodes of ischemic ST segment depression were detected in 50 patients (52%) with angina and 9 control subjects (9%). In patients with angina, 159 episodes (71%) were silent, median duration of ischemia was 66 min (range 1 to 782) and mean ± SB ST depression was 2.4 ± 1.1 mm. In logistic regression analysis, serum cholesterol (p < 0.05) and ischemia on exercise (p < 0.01) were independently associated with the presence of ambulatory ischemia in men with angina, but only the latter was significant in women; this may reflect a different pathophysiologic basis for ambulatory ischemia in women. During follow-up, there were 29 events. Kaplan-Meier survival analysis revealed no significant difference in event-free survival between patients with angina who did and did not have ischemic episodes (66% vs. 72%, p = NS).Conclusions. This is the first study representative of new patients with angina pectoris in the general population and shows that ischemia during daily living activities is present in >50% of these patients but appears to be of no prognostic value.

Atrial Natriuretic Factor Release during Transient Myocardial Ischemia: A Placebo-Controlled Study in Man

Atrial natriuretic factor (ANF) exerts a vasodilatory effect on the coronary bed in myocardial ischemia. Besides wall stretch, ANF release can also be triggered by endothelin in experimental models. We studied the time course of ANF release and its relationship with endothelin during transient myocardial ischemia in man. Twelve patients subjected to the dipyridamole echocardiography test (DET) in a single-blind, randomly balanced, placebo-controlled setting were studied. Circulating ANF and endothelin were monitored during both dipyridamole and placebo. Dipyridamole caused left ventricular (LV) dyssynergy in 6 patients (group 1: multiple or isolated coronary artery stenosis) and acute left atrial dilation in 5 out of 6. In these 5 patients, a progressive rise of circulating ANF was found soon after LY dyssynergy, starting from time +8 min (55 ± 12 vs. 40 ± 7 at time 0 and 42 ± 8 pmol/1 time-matched placebo, p < 0.05 for both), becoming highly significantly different from + 10 min (72 ± 13 vs. 40 ± 7 at time 0 and vs. 47 ± 5 pmol/1 time-matched placebo, p < 0.01 for both) up to the end of the study (+40 min). Circulating ANF and echocardiographie parameters did not vary in the other 6 patients undergoing the DET (group 2) as well as during placebo in both groups. The DET caused heart rate and the rate-pressure products to increase to the same extent in both groups (+12 and +13%; +13 and +15%, respectively). Circulating endothelin did not vary. The consistent and long-lasting rise of circulating ANF in patients with coronary artery disease during transient myocardial ischemia indicate that ANF measurements during chest pain may be an important marker of the reduction in myocardial perfusion and LV dysfunction. Further studies will indicate if ANF may play a physiological role to attenuate anginal attacks.

The influence of clinical intervention on pressure-volume relationships--the conductance (volume) technique.

We analysed end-systolic pressure-volume relations (ESPVR), using the conductance technique, to study the potential inotropic effects of (1) PDE inhibitor drugs, (2) class 1 anti-arrhythmic drugs and (3) PTCA-induced myocardial ischaemia (MIS). The question of contractility involvement is of clinical importance, since with inotropy-induced rise in MVO2 there is a risk of MIS, should any of the cardiotonic drugs (amrinone, enoximone, piroximone) be used in patients with CAD. Accordingly, we analysed their haemodynamic effects, identified improved contractility as one factor of these drugs' mode of action and proved their inability to induce MIS. Anti-arrhythmic drugs may cause cardiodepression, a risk theoretically well recognized but clinically poorly defined. We monitored the haemodynamics of six class 1 anti-arrhythmic drugs and found that drug-induced moderate impairments of contractility (at rest and during tachycardia) proved significant, but clinically asymptomatic, and did not differ significantly from drug to drug. PTCA provides routine models of MIS in man. We analysed ESPVR and haemodynamics during MIS with PTCA and coronary angiography (CORO) and the induced diminished LV function during CORO v PTCA appeared quantitatively less. Inotropy impairment was rather modest during ischaemia: dP/dtmax was reduced by 11%, slope k of the ESPVR by 14%, while the EDV was increased by 67%. All changes were reversible about 90 s after PTCA balloon occlusion and 20 s after CORO.

New insights into the management of myocardial ischemia

Episodes of ST depression are closely related to transient decreases in regional myocardial perfusion during physical or mental stress. At the on-set of these events, there is transient constriction of atherosclerotic stenoses, with an increase in myocardial demand as reflected by increases in heart rate and blood pressure. Recent research has shown that normal epicardial coronary arteries respond to these provocations and to increasing blood flow with progressive vasodilation. In contrast, atherosclerotic vessels lose this ability to dilate and may show paradoxical constriction. This abnormal constriction parallels the response of the arteries to acetylcholine, which can be used to assess the ability of the coronary endothelium to regulate vasodilation. The loss of endothelium-dependent vasodilation appears to be an important functional manifestation of coronary atherosclerosis and a potential triggering mechanism for transient ischemia. Dysfunctional endothelium may also result in a procoagulant surface, with cell adherence and local thrombus formation. Restoration of normal endothelial function is likely to emerge as an important therapeutic objective in the management of myocardial ischemia and coronary atherosclerosis.

Mathematical modeling of the efflux kinetic of enzyme- and structure proteins in serum following acute myocardial ischemia in man

Mathematical modeling of the efflux kinetic of enzyme- and structure proteins in serum following acute myocardial ischemia in man

Silent myocardial ischemia in men with systemic hypertension and without clinical evidence of coronary artery disease

The prevalence, characteristics and circadian pattern of silent myocardial ischemia, and its association with ventricular arrhythmias was studied in hypertensive men aged 35 to 70 years (mean 61) without clinical cardiac disease. Participants were withdrawn from diuretic treatment and received 1 month of oral electrolyte repletion with 40 mmol of potassium chloride, and 400 mg of magnesium oxide daily. Twenty-four-hour Holter monitoring was then performed. Episodes of silent myocardial ischemia occurred in 50 of 186 men (27%) and lasted from 2 to 289 minutes (mean 30 and median 18). Statistical analysis comparing the interval from midnight to 6 A.M. with each of the other three 6-hour time intervals revealed that participants were less likely to have silent myocardial Ischemia in this period (p < 0.01 for each comparison) than at other times of the day. There was little difference in the proportion of men with a frequent or complex ventricular arrhythmia during the entire day or within 1 hour of the silent myocardial ischemic episode (or during a comparable time period) comparing those with to those without silent myocardial ischemia. These findings indicate that silent myocardial ischemia occurs in approximately 25% of an older population of hypertensive men without history of symptomatic cardiac disease. The circadian pattern of frequency of silent ischemic events in men free of clinical cardiac disease is similar to that reported for patients with cardiac disease and coincides with that reported for sudden death. There was no significant association between silent myocardial ischemia and ventricular arrhythmias.

Exercise-Induced Myocardial Ischaemia in Men with Angina is Improved by a New Compound with Alpha-2 Adrenoceptor Agonist Activity

Exercise-Induced Myocardial Ischaemia in Men with Angina is Improved by a New Compound with Alpha-2 Adrenoceptor Agonist Activity

Exercise-induced myocardial ischaemia in men with angina is improved by a new compound with alpha-2 adrenoceptor agonist activity

Exercise-induced myocardial ischaemia in men with angina is improved by a new compound with alpha-2 adrenoceptor agonist activity

Elevation of plasma neuropeptide Y‐like immunoreactivity and noradrenaline during myocardial ischaemia in man

Plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline were studied for 25 h in 22 patients with acute ischaemic heart disease. On admission, NPY-LI levels were above normal in 16 patients, and 20 patients had increased noradrenaline levels. The initial plasma NPY-LI did not differ between patients with acute myocardial infarction (AMI) and angina pectoris. Initial plasma noradrenaline levels were higher in patients with AMI than in those with angina pectoris. Plasma levels of noradrenaline remained elevated in AMI patients, but decreased towards normal values in patients with angina pectoris. Levels of NPY-LI returned to normal within 25 h in all patients. Tachycardia and left ventricular failure were related to high NPY-LI and noradrenaline levels. A positive correlation was found between noradrenaline and NPY-LI in plasma. It is suggested that neuropeptide Y (NPY), an endogenous vasoconstrictor peptide, should be considered as one of the mediators involved in the cardiovascular response to sympathetic activation induced by myocardial ischaemia.

Ability of calcium-entry blockade by felodipine to disclose different pathogenetic mechanisms behind hyperventilation-induced myocardial ischemia in men

To verify that myocardial ischemia occurring during ither the overbreathing or recovery phase of the hyperventilation test is based on different pathogenetic mechanisms, 2 consecutive series of patients, selected on the basis of their response to a run-in hyperventilation test, were studied. Group I comprised 15 patients who developed ST-segment depression early during overbreathing, whereas group II consisted of 12 patients showing ST-segment depression late during the recovery phase. A single oral dose of felodipine 10 mg or of placebo was administered on 2 consecutive days according to a randomized, double-blind, crossover design, and the hyperventilation test was repeated, on both days of the study, 3 to 5 hours after drug intake. In group I, ST-segment depression occurred after placebo in all patients during overbreathing, with an increase in rate pressure product (from 112 ± 31 at baseline to 168 ± 55 mm Hg × beats/min/100 at the onset of ST-segment depression; p < 0.01). After felodipine, 13 patients continued to show ST-segment depression during overbreathing, together with an increase in rate pressure product (from 107 ± 24 at baseline to 158 ± 46 mm Hg × beats/ min/100 at the onset of electrocardiographic changes; p < 0.01). In group II, all 12 patients showed ST-segment depression during recovery after placebo, with a rate pressure product comparable to baseline conditions (112 ± 35 at baseline vs 102 ± 27 mm Hg × beats/min/100 at the onset of ST-segment depression; difference not significant). After felodipine, no patient developed ST-segment depression or chest pain. These findings confirm that early hyperventilation-induced ST-segment depression is related to increased oxygen consumption, which cannot be prevented by felodipine. On the other hand, felodipine is highly effective in preventing delayed ischemia, which is due to a primary reduction in coronary blood flow.

Autonomic nervous system activity during myocardial ischemia in man estimated by power spectral analysis of heart period variability

Ambulatory patients with coronary artery disease exhibit a nearly universal increase in heart rate during episodes of ST depression. 1 The cause of the increase in heart rate presumably represents an increase in sympathetic nervous activity, a decrease in parasympathetic nervous activity, or both. The purpose of this investigation was to determine the cause of increased heart rate during ambulatory ischemic episodes using power spectral analysis of normal RR intervals. An increase in sympathetic nervous activity causes an increase in low frequency power and an increase in the low to high frequency ratio. A decrease in parasympathetic nervous activity causes a decrease in both low and high frequency power, that is, no change or a decrease in the low to high frequency ratio.

Amiodarone induced rate-related QRS widening during myocardial ischemia in man

Amiodarone induced rate-related QRS widening during myocardial ischemia in man

Balloon occlusion during coronary angioplasty as a model of myocardial ischaemia: reproducibility of sequential inflations.

In order to evaluate the potential of balloon occlusion during coronary angioplasty as a model of myocardial ischaemia in man we have measured coronary sinus blood flow (CSBF), myocardial oxygen consumption (MVO2), lactate extraction (LER) and electrocardiographic changes in 11 patients undergoing left anterior descending artery (LAD) angioplasty. Baseline measurements were made before balloon crossing and between inflations. Four consecutive inflations each of 60 s duration were made; 5 min return to baseline was allowed between inflations. There was a significant reduction in CSBF and MVO2 (ml min-1) during inflations 2, 3 and 4 (CSBF: 121 +/- 66----94 +/- 53, 113 +/- 49----99 +/- 42, 124 +/- 66----102 +/- 41, P less than 0.02; MVO2: 11.3 +/- 6.6-9.1 +/- 3.9, 10.4 +/- 3.7-8.7 +/- 2.4, 12.2 +/- 4.4----9.4 +/- 2.8, P less than 0.05). However during the first period of balloon occlusion there were inconsistent changes in coronary flow with an overall rise in mean flow (97 +/- 35----128 +/- 80 ml min-1, P = NS) and an overall rise in mean myocardial oxygen consumption (9.6 +/- 3.8----12.5 +/- 7.5 ml min-1, P = NS). There was lactate production during all four inflations but the changes during the first one did not achieve statistical significance. These inconsistent changes during the first inflation were thought to be due to partial obstruction of the stenosis by the deflated balloon before primary dilatation. The changes due to crossing and during the first two inflations were further investigated in another group of 12 patients undergoing LAD angioplasty. Great cardiac vein flow (GCVF), CSBF, MVO2 and LER were recorded at baseline, during crossing and during the first two inflations. With the deflated balloon across the stenosis there were no changes in CSBF or MVO2 but there was a fall in GCVF (103 +/- 28----77 +/- 50, P = NS) and a significant fall in LER (77 +/- 57----16 +/- 37, P less than 0.01). Although there was a fall during the first inflation in CSBF, GCVF, MVO2 and lactate extraction none of these changes were significant. During the second inflation these changes were of greater magnitude and achieved statistical significance. While balloon occlusion during coronary angioplasty has the potential of providing a model of ischaemia in man we have found the first inflation period unreliable, due to the variable degree of occlusion by the deflated balloon. We suggest that only subsequent inflations after the primary dilatation are used for observations.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of drug therapy on the ischemic response to acute coronary occlusion in man: Supply-side economics

Recent advances in the management of acute COTOnary occlusion have given new importance to the effects of drug therapy during limited or intermittent periods of coronary occlusion. The influence of drugs during ischemia may permit therapy selection designed to limit ischemic sequelae and potential infarct size. In man, the ischemic responses to sudden increases in myocardial demand have been extensively studied, usually to assess clinical and mechanistic effects of various antianginal therapies. However, the study of ischemia due to a sudden decrease in myocardial oxygen supply has been restricted to a few patients with severe coronary spasm. After considerable clinical experience, percutaneous transluminal coronary angioplasty can now be used as a unique, controlled model of transient myocardial ischemia in man, permitting simultaneous examination of systemic and coronary hemodynamics, left ventricular function, and subsequent responses to commonly used drugs in the treatment of myocardial ischemia. Analysis of drug effects during acute supply-limited myocardial ischemia.is important in providing not only safer and potentially improved coronary interventional techniques, but also for understanding mechanisms limiting ischemia in the early periods of acute myocardial infarction or during episodes of coronary artery spasm. This review will examine thz supply-side economics of myocardial ischemia, concentrating on the differences between “supply” and “demand” types of ischemia and identifying the significant and consistent sequence of pathophysiologic ischemic events.

Coronary sinus pH during percutaneous transluminal coronary angioplasty: early development of acidosis during myocardial ischaemia in man.

Coronary sinus pH was measured continuously in eight patients undergoing angioplasty to the left anterior descending coronary artery. A catheter tip pH sensitive electrode with a response time of less than 300 ms and an output of greater than or equal to 57 mV/pH unit was placed high in the coronary sinus. Recordings were obtained during a total of 24 balloon occlusions of the left anterior descending coronary artery varying in duration from 5 to 45 s. Continuous 12 lead surface electrocardiograms were recorded. During or after balloon inflation of greater than or equal to 12 s (n = 4) there was no change in coronary sinus pH or the electrocardiogram. During balloon inflation of greater than or equal to 15 s (n = 20) coronary sinus pH was unaltered but between 4 and 6 s after balloon deflation coronary sinus pH fell transiently by between 0.010 and 0.120 pH units before returning to the control value within 65 s. Ischaemic changes were seen on the electrocardiogram during 15 balloon occlusions. In individual patients the peak fall in coronary sinus pH was related to the duration of occlusion of the left anterior descending coronary artery. A rise in coronary sinus pH (alkalosis) was never seen. In man acidosis occurs in the myocardium after short periods (greater than or equal to 12 s) of ischaemia. The fall of pH precedes ischaemic changes on the surface electrocardiogram and occurs concurrently with the earliest reported changes in contractile function.

CORONARY ARTERY INFUSION OF NEUROPEPTIDE Y IN PATIENTS WITH ANGINA PECTORIS

Neuropeptide Y was infused into a coronary artery of 6 patients with typical angina but no significant coronary stenosis. 3 patients had transient myocardial ischaemia, shown by typical pain and electrocardiographic change, at doses of 0·2 pmol/kg per min in 2 patients and 1·0 pmol/kg per min in 1 patient. The arteriographic appearances suggested constriction of small vessels rather than constriction of epicardial coronary arteries. The ischaemia was completely reversed by intracoronary administration of isosorbide dinitrate with no adverse sequelae. This is the first demonstration of myocardial ischaemia in man induced by a peptide neurotransmitter.

ESC Postgraduate Teaching Programme: Report from a graduate course on ‘Management of myocardial ischaemia’, Thoracic Clinics, Karolinska Hospital, Stockholm, 12—14 June 1986

ESC Postgraduate Teaching Programme: Report from a graduate course on ‘Management of myocardial ischaemia’, Thoracic Clinics, Karolinska Hospital, Stockholm, 12—14 June 1986

Hypoxanthine and lactate release and intracoronary distribution changes of krypton-81M during myocardial ischemia in man

Hypoxanthine and lactate release and intracoronary distribution changes of krypton-81M during myocardial ischemia in man