Myocardial Lactate Metabolism Research Articles

Effect of coronary by-pass surgery on myocardial lactate metabolism

Effect of coronary by-pass surgery on myocardial lactate metabolism

Lactate release during the recovery period of pacing-induced angina in assessment of myocardial ischaemia.

Myocardial lactate (L) metabolism was tested in 27 stable angina patients during atrial pacing (AP) and in the recovery period (R) from AP-induced angina pectoris. The recovery period was assessed in order to evaluate the changes in the rate of L release and detect possible relationships with the severity of ischaemic damage. The following variables were assessed: coronary sinus blood flow (CSBF), left ventricular end-diastolic pressure (LVEDP), lactate extraction ratio (L%), lactate extraction or release rate (LR) and myocardial oxygen consumption (MVO2) at the onset of AP (AP1), during angina (AP2), and 30 s, 2 and 4 min (R1, R2 and R3) after AP ceased. At Ap2, negative L% and LR values (-39.37 +/- 43.3, -3.2 +/- 2.9) were found, in spite of a rise in CSBF (+86%, P less than 0.001). Furthermore, LVEDP showed its maximal increase in AP2 (+27%, P less than 0.001). Compared to AP2, L% resulted unchanged in R1, while LR showed a mild decrease (from -3.2 +/- 2.9 to +2.06 +/- 2.93). Lactate production was converted to extraction in R3 only. Since lactate production and release are progressively reduced with increasing severity of ischaemic damage, AP2 coronary sinus lactate release should largely arise from the less damaged areas (i.e. the outer myocardial layers) and the contribution of the more damaged areas (i.e. the inner myocardial layers) should be more limited. After AP ceases, the mild ischaemic areas should recover more rapidly than the severely ischaemic areas, where the damage only declines, leading to a temporary increase in lactate production and release.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of intravenous dipyridamole combined with pacing stress for detection of myocardial ischemia in coronary artery disease.

In order to establish a more clinically useful diagnostic method to detect myocardial ischemia, a stress test of 0.56 mg/kg of intravenous dipyridamole (D), an atrial pacing (P) and the combination of both (D + P) were administered to 14 patients with significant coronary stenosis and 8 patients with normal coronary arteriogram. The effects on regional coronary hemodynamics and myocardial metabolism were subsequently studied. Treadmill exercise tests in 15 patients and thallium-201 exercise myocardial scintigraphy in 14 patients were also performed at another time. When the uptake ratio of myocardial lactate less than 0% was used as an indicator of myocardial ischemia, 100% (12/12) of sensitivity and 100% (6/6) of specificity were obtained with (D + P)-test in diagnosis of significant coronary stenosis and its sensitivity was significantly higher than that with P-test (43%) or with D-test (31%). Even though sensitivity and specificity of exercise electrocardiogram (70% and 50%) or thallium-201 exercise myocardial scintigram (88% and 80%) in diagnosis of coronary stenosis were not significantly lower than those of (D + P)-test respectively, myocardial ischemia could also be detected with (D + P)-test in two patients at the region perfused by the infarct-related artery, which had not been detected by thallium-201 exercise myocardial imaging. We conclude, (D + P)-test combined with investigation of myocardial lactate metabolism is quite useful to detect myocardial ischemia.

Cardiac metabolism and coronary hemodynamics before and after bypass surgery for anomalous origin of the left main coronary artery from the pulmonary trunk

In patients with anomalies of the coronary arteries, beneficial results have been reported after surgery with regard to ischemic symptoms, left ventricular size and contractility, thallium scintigrams and exercise stress testing. 1–4 We describe a patient who had ventricular fibrillation due to anomalous origin of the left main (LM) coronary artery from the pulmonary trunk (PT). The exercise electrocardiogram (ECG) continued to show ST depression after bypass surgery, although repeat arteriography showed an open graft; however, myocardial lactate metabolism normalized and coronary sinus blood flow (CSBF) doubled, indicating improved myocardial oxygen supply.

Hemodynamic Consequences of Halothane Anesthesia during Chronic Anemia

The hemodynamic effects of halothane anesthesia in chronically anemic mongrel dogs were evaluated. Control and anemic animals (13.7 +/- 0.4 g/dl hemoglobin mean +/- SE vs. 3.4 +/- 0.3 g/dl) were exposed to 0.75, 1.5, and 2.25% inspired halothane and changes in cardiac output (CO), heart rate (HR), dp/dt, heart work, heart efficiency, myocardial oxygen consumption (MVO2), mean arterial blood pressure (MABP), central venous pressure (CVP), left ventricular end-diastolic pressure (LVDP), left coronary blood flow (CBF), systemic vascular resistance (SVR), and myocardial lactate metabolism were measured and compared. Anemic dogs showed a significantly lower SVR at each halothane dose when compared with controls. In addition, SVR progressively decreased with increasing halothane in anemic dogs, while SVR remained unchanged in controls. CO, CBF, MVO2, and heart work all were significantly greater in anemic canines compared with controls with each halothane concentration. Heart efficiency, dp/dt, HR, and MABP were not significantly different in anemic and control dogs. Neither control nor anemic dogs demonstrated myocardial hypoxia as evidenced by a lack of myocardial lactate production. The results from this study suggest that anemic animals appear to tolerate large concentrations of halothane.

Coronary sinus lactate estimation and esophageal motor anomalies in angina with normal coronary angiogram.

Twenty-three patients (ages 44-82) with angina-like chest pain with a negative stress test and a normal coronary angiogram were studied for myocardial lactate metabolism during atrial pacing and for esophageal motor function with manometric measurements and acid infusion test. Eight patients had an abnormal myocardial lactate metabolism during maximal atrial pacing. Esophageal motor anomalies were observed in six of these eight patients and nine of the 15 subjects with normal myocardial lactate metabolism. The frequency and type of these anomalies were not different between the two groups of patients. Perfusion of acid into the esophagus reproduced the spontaneous pain syndrome in three patients, independent of any simultaneous motor dysfunction. These results suggest that esophageal motor anomalies must be interpreted with caution in patients with angina-like chest pain before affirming the exclusively esophageal origin of the pain.

Effects of nifedipine on arterial concentration and myocardial extraction of catecholamines during pacing-induced angina pectoris.

We studied nine patients with arteriosclerotic coronary heart disease (Group I) and 10 patients with normal coronary arteries (Group II) to elucidate mechanisms by which nifedipine affects catecholamine arterial levels and myocardial extraction at rest and during pacing. Nifedipine induced signs of general and coronary vasodilatation and improved myocardial lactate metabolism during pacing. Noradrenaline arterial concentration increased significantly after nifedipine in both groups (p less than 0.01). In Group I, the values were 40-50% higher compared with Group II. The net myocardial extraction of noradrenaline was not significantly affected by nifedipine, except during pacing in Group II, in which an increase in myocardial release was seen (p less than 0.05). In Group I, there was no correlation between arterial concentration of noradrenaline and myocardial release, while there was a significant negative correlation in Group II (p less than 0.0001). Adrenaline arterial concentration and myocardial extraction were not altered by nifedipine, but there was a positive significant correlation in Group I between arterial concentration and myocardial extraction of adrenaline (p less than 0.001). In conclusion, nifedipine increased noradrenaline levels in both groups of patients, probably reflecting a rise in sympathetic activity. Because myocardial lactate production turned into extraction in patients with coronary artery disease, the increased sympathetic tone evidently did not outweigh the beneficial antianginal effects of nifedipine.

Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty.

The response of left ventricular function, coronary blood flow, and myocardial lactate metabolism during percutaneous transluminal coronary angioplasty (PTCA) was studied in a series of patients undergoing the procedure. From four to six balloon inflation procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD) and a total occlusion time of 252 +/- 140 sec. Analysis of left ventricular hemodynamics in 19 patients showed that the relaxation parameters, peak negative rate of change in pressure, and early time constants of relaxation, responded earliest to short-term coronary occlusion (peak effect at 17 +/- 7 sec) while other parameters, such as peak pressure, left ventricular end-diastolic pressure, and peak positive rate of change in pressure, responded more gradually, suggesting a progressive depression of myocardial mechanics throughout the procedure. Left ventricular angiograms, available for 14 patients, indicated an early onset of asynchronous relaxation concurrent with the early response in peak negative dP/dt and the time constant of early relaxation. All hemodynamic functions fully recovered within minutes after the end of PTCA. Mean blood flow in the great cardiac vein and proximal coronary sinus and the hyperemic response were measured in 20 patients. Before PTCA mean flow in the great cardiac vein was 69 +/- 17 ml/min and in the coronary sinus it was 129 +/- 34 ml/min. Reactive hyperemia (great cardiac vein) was 55% after the first PTCA and 91% after the third. A more pronounced reaction was observed when the residual functional coronary stenosis was reduced in subsequent dilatations. Arteriovenous lactate difference appeared constant during the first two occlusions (control +0.11 mmol/liter, first PTCA -0.87 mmol/liter, and second PTCA -0.82 mmol/liter) and did not increase during subsequent occlusions. Within minutes after the procedure lactate balance was again positive, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent dysfunction of global or regional myocardial mechanics, myocardial blood flow, or lactate metabolism after PTCA with four to six coronary occlusions of 40 to 60 sec.

Myocardial lactate metabolism during pacing induced angina pectoris

Myocardial lactate metabolism during pacing induced angina pectoris

Myocardial lactate metabolism during pacing induced angina pectoris

Myocardial lactate metabolism was studied in 20 patients with coronary heart disease during and immediately after slight angina pectoris induced by atrial pacing. Myocardial lactate extraction ratio (MLE) decreased from 0.27 +/- 0.03 (SEM) before angina to 0.01 +/- 0.06 during angina, and further to -0.32 +/- 0.11 at 15 sec after pacing. Lactate production was found to occur in eight patients during pacing and 13 patients after pacing. Cardiac venous flow was measured by thermodilution in eight of these patients. 'Net ischaemic lactate efflux' increased by 23 +/- 4 mumol/min 15 sec after pacing, whereas 'lactate uptake in non-ischaemic regions' diminished by 11 +/- 2 mumol/min. Lactate production 15 min after pacing was revealed in all patients with subtotal stenosis of the left anterior descending coronary artery (LAD), whereas it was less frequently observed in patients with occluded LAD and collaterals to the post-stenotic area. Increased washout of metabolites from the ischaemic myocardium during the early recovery period is the main reason for the rather high sensitivity of ischaemia detection by this procedure. This permits shorter pacing periods and less pain than in earlier studies. Both MLE and electrocardiographic changes were equally reproducible after 20 and 45 min recovery period.

Captopril in congestive heart failure: Improved left ventricular function with decreased metabolic cost

The oral angiotensin-converting enzyme inhibitor captopril (CPT) produces beneficial hemodynamic and clinical responses in patients with chronic congestive heart failure (CHF). Cardiac output and stroke volume increase, along with a decrease in pulmonary capillary wedge pressure, indicating improved left ventricular function. During maintenance CPT therapy, the beneficial hemodynamic and clinical effects appear to be sustained. Improved left ventricular pump function with CPT is associated with decreased metabolic cost, as myocardial oxygen consumption consistently decreases in proportion to the decrease in myocardial oxygen demand. Myocardial ischemia occurs infrequently, as is evident from the abnormal myocardial lactate metabolism. Hypotension appears to be the major adverse effect, particularly after the first dose. However, with dose titration and the use of a smaller initial dose, a marked precipitous fall in blood pressure can be avoided in the majority of patients. Thus, CPT may prove to be a useful agent in the vasodilator therapy of chronic CHF.

Left ventricular O2 requirements of pressure and volume loading in the normal canine heart and inaccuracy of pressure-derived indices of O2 demand.

The purpose of this study was to: 1) re-evaluate the left ventricular O2 requirements (MVO2) of pressure and volume-loading; and b) assess the accuracy of pressure-derived indices of left ventricular (LV) O2 demand under pressure-loading and volume-loading conditions. Using a right heart bypass preparation (heart rate 150 beats . min-1), mean arterial pressure (7.3 to 22.9 kPa) and cardiac output (0.8 to 6.0 litre . min-1) were varied independently. Adequate left ventricular O2 supply was demonstrated by normal transmural distribution of blood flow, normal myocardial lactate metabolism, and intact reactive hyperaemic responses. For equivalent increases in cardiac external work (from 2 to 4 joules . min-1) pressure-loading and volume-loading resulted in similar increases in O2 uptake (59% and 49%, respectively, P = 0.21). MVO2 was consistently greater for volume-loading than for pressure-loading at any SPTI, pressure-rate product, and triple product. The prediction of O2 demands by these indices under these loading conditions collectively was unreliable (r = 30 to 0.42). O2 requirements of the left ventricle with both pressure-loading and volume-loading were highly correlated (r = 0.82 to 0.99) with meridional wall stress. We conclude that: 1) volume-loading conditions have a greater O2 requirement than appreciated previously; 2) pressure loads and volume loads require similar O2 uptake in the normal canine heart for similar external work; 3) currently used pressure-derived indices are unreliable predictors of LV O2 demand when loading conditions are varied; and 4) O2 requirements are more uniformly related to meridional wall stress.

The effect of pindolol on myocardial blood flow, metabolism and function during rest and pacing in patients with coronary heart disease.

1 The study was designed to elucidate further the mechanism by which beta-adrenoceptor antagonism with pindolol relieves the symptoms of angina pectoris in patients with coronary heart disease. 2 Pindolol administration was associated with an elevated threshold for angina pectoris and improved myocardial lactate metabolism during supraventricular pacing. 3 This beneficial effect of pindolol was independent of changes in myocardial blood flow and was not mediated by haemodynamic effects. 4 The results suggest that in angina pectoris, in addition to the recognized beneficial effects of beta-adrenoceptor blockade, the actions of pindolol also result from, as yet, poorly described phenomena such as redistribution of myocardial blood flow or metabolic effects.

Continuous myocardial bloodflow distribution imaging in man with krypton 81 m intracoronary : Correlation with myocardial lactate metabolism during single and repetitive periods of myocardial ischemia

Continuous myocardial bloodflow distribution imaging in man with krypton 81 m intracoronary : Correlation with myocardial lactate metabolism during single and repetitive periods of myocardial ischemia

Effects of new calcium channel blocker of niludipine on the coronary hemodynamics, diastolic properties, and metabolic responses to tachycardia stress in patients with coronary disease.

A new calcium channel blocker, niludipine, was administered intravenously to nine patients with coronary artery disease in order to investigate its effects on left ventricular systolic and diastolic function, coronary sinus blood flow, and myocardial lactate metabolism. Coronary sinus pacing was performed in all patients and produced angina in six patients. Niludipine increased the resting heart rate from 75+/-3 beats/min (mean+/-SEM) to 82+/-3 (NS) and decreased the left ventricular systolic pressure from 155+/-4.7 mm Hg to 134+/-2.8 (p less than 0.05). Coronary sinus blood flow increased by 9%(NS). During pacing after niludipine, clinical improvement occurred in the six patients who had initially experienced angina. The extent of ischemic ST segment depression was decreased (-1.56+/-0.27 mm to -0.78+/-0.38, p less than 0.02) and myocardial lactate metabolism was improved. When pacing was terminated, niludipine suppressed the elevation of left ventricular end-diastolic pressure compared to pretreatment values (16.2+/-2.5 mm Hg vs 8.5+/-0.9, p less than 0.05) and decreased the left ventricular time constant T(26.4+/-3.6 msec to 20.2+/-2.4 p less than 0.05). The results suggest that niludipine appears to be beneficial in reducing systolic and diastolic work of the left ventricle during pacing induced angina without a significant change in total coronary sinus blood flow. Niludipine appears to have less of a hypotensive and reflex tachycardic effect than nifedipine.

Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man.

Myocardial blood flow has been recognized to be heterogeneous in patients with coronary artery disease. Traditional arterial-coronary sinus sampling methods cannot demonstrate comparable heterogeneity of myocardial metabolism. In this study we used a tracer technique to investigate possible heterogeneity of myocardial lactate metabolism. Twenty-one patients with symptoms of ischemic heart disease were studied. We injected 14C-1-lactate intravenously as a constant infusion after a priming dose. Coronary sinus and arterial samples were obtained for chemical and radioisotopic analyses. At rest, myocardial lactate extraction by chemical analysis was 24.6 +/- 8.5% (mean +/- SD). By radioisotopic analysis, the lactate extraction was 41.0 +/- 10.2% (p less than 0.001). Thus, certain areas of the myocardium were releasing lactate despite global net extraction of lactate. In the 12 patients with significant left main or both left anterior descending (LAD) and left circumflex (LCX) lesions, the calculated amount of lactate released at rest was 0.136 +/- 0.045 mumol/ml of blood (mean +/- SD). In contrast, the amount released in the six patients with a significant lesion in only the LAD or LCX was 0.076 +/- 0.019 mumol/ml, and in the three patients without left coronary arterial lesions it was 0.039 +/- 0.004 mumol/ml. Using a tracer method, myocardial lactate metabolism was demonstrated to be heterogeneous at rest in patients with ischemic heart disease. A significant amount of lactate can be released by the myocardium at a time when chemical arterial-coronary sinus analysis indicates global myocardial extraction. The amount of lactate released appears to be related to the severity of the coronary artery disease.

Is there any Benefit from Adding Single-Dose Cardioplegia to Topical Cooling of the Ischaemic Myocardium in Aortic Valve Replacement Operations?

The myocardial oxygen extraction, lactate metabolism and cardiac performance were studied after topical cold myocardial ischaemia (TCI) with or without associated cold potassium cardioplegia (CPL) in aortic valve replacement (AVR) patients. There were no such differences between the CPL + TCI-group and the TCI-group in the postischaemic coronary sinus blood oxygen tension, coronary sinus blood haemoglobin oxygen saturation, arterial-coronary sinus blood oxygen content difference, arterial-coronary sinus blood lactate difference, CI-PCWP or LVSWI-PCWP relationship that could be attributed to the cardioplegia. The coronary sinus blood oxygen values did not indicate any gradually developing postischaemic disturbances in the myocardial oxygen utilization. There was, however, a marked myocardial lactate washout and production in both groups five and ten minutes after initiation of reperfusion after ischaemia. There was a marked increase in the CI after bypass in the CPL + TCI-group, and the cardiodepression at late post-operative stages was minimal in both groups according to the CI-PCWP and LVSWI-PCWP relationship. These results suggest that the topical cooling technique used provides a degree of protection of the myocardial energy metabolism and function that cannot be further improved by adding single-dose cardioplegia by means of the direct coronary cannulation method used here.

Does normothermia afford better conditions for myocardial oxygenation than hypothermia during artificial coronary perfusion? A clinical study of aortic valve replacement patients.

Myocardial oxygenation and lactate metabolism, changes in haemoglobin oxygen affinity and postoperative myocardial recovery were studied during normothermic (NCP) and hypothermic (HCP) coronary perfusion in association with aortic valve replacements. The P50 values were maintained at prebypass levels in the NCP-group, but were significantly lower in the HCP-group than in the NCP-group during and after bypass. This was reflected in a greater oxygen extraction from the haemoglobin by the myocardium only after bypass. During coronary perfusion, the arterial-coronary sinus oxygen content difference decreased by about 70% and the coronary sinus blood PO2 and oxygen saturation increased by about 60% and 80%, respectively. During rewarming after hypothermia in the HCP-group there was a marked lactate production by the myocardium in 3 out of 8 patients. After bypass the myocardial oxygen extraction was only slightly diminished as compared to the preoperative control in both groups. At this stage ne signs of defec...

Propranolol during the evolution and subsequent ten days of myocardial infarction in man: hemodynamic, initial cardiac energetic, and neurohumoral responses.

AbstractDuring the evolution of transmural myocardial infarction an intensive sympathetic hyperactivity was observed. Plasmal‐norepinephrine and epinephrine contents were strikingly increased, the mean values to 2.047±1.10 (SD) and 0.947±0.48 μg/l, respectively. Propranolol (0.1 mg/kg) was administered intravenously within an average of 8.8 h of transmural myocardial infarction to 55 patients who did not show significant left ventricular failure. The drug was continued orally with an average dose of 567±20 (SD) mg q6h for 10 d. Mean plasma propranolol levels during the first 5 d ranged between 89 and 162 ng/ml. Cardiac index, left ventricular ejection fraction, and, to a lesser degree, blood pressure significantly decreased. Mean pulmonary capillary wedge pressure remained unchanged. Decreases in coronary blood flow and myocardial oxygen consumption were associated with improvement of myocardial lactate metabolism, suggesting reduced myocardial oxygen requirements. Plasma free fatty acid contents significantly decreased. Myocardial glucose extraction and respiratory quotient increased, indicating enhanced carbohydrate utilization. Prior to propranolol administration, plasma glucose and glucagon contents were increased and plasma insulin levels were inappropriately low. Initial glucagon and initiall‐norepinephrine and epinephrine contents were correlated (r = 0.54 and 0.50, p <0.01). Beta‐adrenergic blockade decreased plasma insulin contents in spite of hyperglycemia and abolished the correlation between glucagon and catecholamines. Propranolol was tolerated well by all patients; none of them developed acute left ventricular failure.The study demonstrates that propranolol can be safely administered during the evolution and early phase of transmural myocardial infarction, if selection criteria for patients are carefully considered. Propranolol, dampening the response to acute ischemic stress, diminishes energy requirements and thus appears to be a promising drug for preservation of ischemic myocardium.

Exercise tests, atrial pacing, and myocardial lactate extraction in relation to coronary arteriography in young patients with angina pectoris

An exercise ECG and atrial pacing with a simultaneous study of myocardial lactate metabolism were used in conjunction with coronary arteriographies for the examination of 33 women and 22 men aged 40 or below whose working capacity was impaired by angina pectoris. Most of the patients fell into the age group 36 to 40. The men with coronary changes had come for examination in a shorter time than other patients. Coronary artery narrowings were found in five women and six men. The findings in other tests were pathological with greater frequency in patients with coronary stenosis. When evaluated on the basis of coronary arteriograms, the exercise and lactate tests proved to be reasonably sensitive (66.6 per cent) and specific (56.3 per cent and 68.8 per cent) in men. In women the sensitivity was high (80 per cent), but the specifivicity low (exercise 35 per cent, pacing 14.3 per cent, and lactates 38.5 per cent, respectively). The pacing ECG was also highly unspecific in men (37.5 per cent). Seven patients gave totally normal findings. The examination did not identify any specific group of patients with changes as indicatives of a constitutional disease of the myocardium. The coronary changes indicated that even in this age it is proper to obtain arteriograms in patients with low working capacity even in the absence of any other changes that angina pectoris itself. There are more false-positive findings in women than in men in exercise tests, and in many situations arteriography assures the best basis for further measures.