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.     

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.     

Potassium exchange in the human heart during atrial pacing and myocardial ischaemia

Potassium homoeostasis in the heart was studied during atrial pacing in 20 patients undergoing diagnostic coronary angiography. The potassium concentrations in the coronary sinus and a systemic artery were recorded continuously by means of catheter tip potassium electrodes. Ten patients with coronary artery disease and a positive exercise test developed chest pain and ST segment depression on the electrocardiogram during atrial pacing. Potassium concentrations in the coronary sinus rose initially and increased further when myocardial ischaemia developed. Ten patients including five with normal coronary arteries remained symptom free during atrial pacing with no electrocardiographic changes. In these patients coronary sinus potassium concentration increased at the onset of pacing, but returned to near control values despite continued pacing. In both groups arterial potassium concentration remained constant. Immediately after the end of pacing there was an abrupt transient fall in potassium concentrations in the coronary sinus to below control values. These results indicate that in man, as in other species, an increase in heart rate causes the transient movement of potassium out of the cell into the extracellular space. The onset of myocardial ischaemia is associated with a further loss of potassium from the cell. The end of pacing or ischaemia is accompanied by a re-uptake of potassium by heart muscle.     

Potassium exchange in the human heart during atrial pacing and myocardial ischaemia.

Potassium homoeostasis in the heart was studied during atrial pacing in 20 patients undergoing diagnostic coronary angiography. The potassium concentrations in the coronary sinus and a systemic artery were recorded continuously by means of catheter tip potassium electrodes. Ten patients with coronary artery disease and a positive exercise test developed chest pain and ST segment depression on the electrocardiogram during atrial pacing. Potassium concentrations in the coronary sinus rose initially and increased further when myocardial ischaemia developed. Ten patients including five with normal coronary arteries remained symptom free during atrial pacing with no electrocardiographic changes. In these patients coronary sinus potassium concentration increased at the onset of pacing, but returned to near control values despite continued pacing. In both groups arterial potassium concentration remained constant. Immediately after the end of pacing there was an abrupt transient fall in potassium concentrations in the coronary sinus to below control values. These results indicate that in man, as in other species, an increase in heart rate causes the transient movement of potassium out of the cell into the extracellular space. The onset of myocardial ischaemia is associated with a further loss of potassium from the cell. The end of pacing or ischaemia is accompanied by a re-uptake of potassium by heart muscle.     

Increased coronary sinus lactate concentration during pacing induced angina pectoris after clinical improvement by glyceryl trinitrate.

Ten patients with stable angina pectoris and obstructed coronary arteries (greater than 75% reduction in diameter) were studied before and during two periods of pacing, the second of which was preceded by sublingual administration of glyceryl trinitrate (mean dose 0.78 mg). Coronary sinus blood flow measurements and aortocoronary sinus blood sampling for metabolite determinations were carried out. Although the rate of pacing was increased by 10 beats/minute after glyceryl trinitrate administration, the onset of angina was delayed in eight patients during pacing. Drug administration decreased coronary sinus blood flow by 42% and myocardial oxygen uptake by 41% during pacing and induced a shift in mean lactate extraction towards a net release (from 3.1% to -12.6%). It increased the number of patients producing lactate from three to five. Glyceryl trinitrate administration decreased myocardial glucose uptake throughout the study, decreased lactate extraction during recovery, and increased the aortocoronary sinus citrate gradient at rest and during recovery, while the exchange of free fatty acids remained unchanged. A decrease in aortocoronary sinus lactate difference during pacing after glyceryl trinitrate administration correlated positively with the fall in coronary sinus blood flow. The metabolic data do not indicate an augmented myocardial lactate production after glyceryl trinitrate administration. A decrease in coronary sinus blood flow seems, therefore, to be of primary importance in explaining the elevated coronary sinus lactate concentration. Our finding that coronary sinus lactate concentration increased during pacing after glyceryl trinitrate administration despite clinical improvement questions the validity of its use as a quantitative index of ischaemia.     

Effects of propranolol on myocardial oxygen consumption, substrate extraction, and haemodynamics in hypertrophic obstructive cardiomyopathy.

Myocardial substrate extraction, coronary sinus flow, cardiac output, and left ventricular pressure were measured at increasing pacing rates before and after propranolol (0.2 mg/kg) in 13 patients with hypertrophic obstructive cardiomyopathy (HOCM) during diagnostic cardiac catheterisation. At the lowest pacing rate myocardial oxygen consumption varied considerably between patients and very high values were found in several individuals (range 10.1 to 57.5 ml/min). These large differences between patients were not explicable by differences in cardiac work; consequently, cardiac efficiency, estimated from the oxygen cost of external work, varied between patients and was lower than normal in all but two. The pattern of substrate extraction at the lowest pacing rate was similar to results reported for the normal heart, and measured oxygen consumption could be accounted for by complete oxidation of the substrates extracted; thus there was no evidence of a gross abnormality of oxidative metabolism, suggesting that low efficiency lay in the utilisation rather than in the production of energy. Each of the four patients with the highest myocardial oxygen consumption and lowest values of efficiency sustained progressive reductions in lactate and pyruvate extraction as heart rate increased, and at the highest pacing rate had low (< 3%) or negative lactate extraction ratios. In three of these four, coronary sinus flow did not increase progressively with each increment in heart rate. One patient with low oxygen consumption and normal efficiency also failed to increase coronary flow with the final increment in heart rate, and produced lactate at the highest pacing rate. Thus the five patients in whom pacing provoked biochemical evidence of ischaemia all had excessive myocardial oxygen demand and/or limited capacity to increase coronary flow. Propranolol did not change lactate extraction significantly at any pacing rate in either the ischaemic or non-ischaemic groups. In only one patient was ischaemia at the highest pacing rate abolished after propranolol, and this was associated with a 30 per cent reduction in oxygen consumption. These results do not demonstrate a direct effect of propranolol upon myocardial metabolism in patients with HOCM, but emphasise the potential value of beta-blockade in protecting these patients from excessive increases in heart rate.     

Systemic and coronary hemodynamic effects of intravenous nicardipine at rest and in ischemia induced by rapid atrial stimulation

The systemic and coronary haemodynamic effects of intravenous nicardipine were investigated in 10 patients with a more than 70 p. 100 stenosis of the left coronary artery. Two brief atrial pacing tests (ST1 and ST2) were performed. ST2 was performed 30 minutes after an intravenous injection of nicardipine 2.5 mg over 5 minutes. Nicardipine produced a 25 p. 100 decrease in ventricular systolic pressure and a substantial increase in cardiac index (from 2.74 +/- 0.48 to 3.46 +/- 0.35 l/min/m2, p less than 0.001). Measurement of the coronary flow rate by the thermodilution method showed a 40 p. 100 increase in sinus blood flow while coronary resistance decreased not only in territories with normal supply but also in myocardial territories distal to the coronary stenosis (from 2.76 +/- 2.3 to 1.83 +/- 1.5 mmHg/ml, p less than 0.02). With the same paced heart rate the ventricular function parameters were significantly improved during ST2 (cardiac index ST2 3.56 +/- 0.65 vs ST1 2.8 +/- 0.48, p less than 0.001; dp/dt max ST2 2143 +/- 369 vs ST1 1874 +/- 301 mmHg/sec, p less than 0.05), reflecting a lower degree of myocardial ischaemia. This was confirmed by the lower amplitude of electrocardiographic depression and by a higher lactate extraction coefficient (LE ST1 6 +/- 7 p. 100 vs LE ST2 12 +/- 12 p. 100, p less than 0.05). Mean arterial blood pressure and coronary sinus blood flow rate values were identical during the two atrial pacing tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Acute Myocardial Ischaemia on Platelet Aggregation in the Coronary Sinus and Aorta in Dogs

The effect of an acute myocardial ischaemia on circulating platelet aggregates (CPA) in the coronary sinus and aorta was studied in open chest dogs. Even before induction of myocardial ischaemia significantly more CPA were found in the coronary sinus than in the aorta. Acute myocardial ischaemia produced by a non-thrombotic coronary artery occlusion increased CPA in coronary sinus, but not in aorta. Administration of acetylsalicylic acid (ASA) reduced the extent of the myocardial ischaemia as evidenced by reduced ST-segment elevations in epicardial ECG. Before induction of myocardial ischaemia, ASA significantly reduced CPA in coronary sinus, but no significant effect was observed during myocardial ischaemia. In the aorta no effect of ASA on CPA was found.     

Differential anti-ischaemic effects of muscarinic receptor blockade in patients with obstructive coronary artery disease; impaired vs normal left ventricular function.

AIMS: In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown. METHODS AND RESULTS: Twenty-four patients who required atropine infusion (to supplement heart rate response) during atrial pacing (pacing was conducted to assess ischaemia as part of an experimental protocol) were studied; 17 patients had normal and seven impaired left ventricular function (ejection fraction < or =0.40). Two control groups were selected from a large database (from patients in whom atrial pacing was carried out but to whom atropine was not administered) to match the normal (n=20) and dysfunction (n=10) groups. In the normal left ventricular function group atropine increased rate pressure product by 12 +/- 4%, as compared to those without atropine (P < 0.05). Left ventricular end diastolic pressure increased less in the atropine group (+40 +/- 8% vs +78 +/- 6%;P < 0.05). Arterial norepinephrine increased similarly in both groups, but coronary flow (as assessed by using a thermodiluting method in the coronary sinus) increased 23 +/ -4% more in the atropine group (P < 0.05). Further, there were lower levels of myocardial lactate production and ST-segment depression in the atropine group [lactate extraction +13 +/- 6% (atropine) vs -19 +/- 4% (controls), ST-segment depression 1. 3 +/- 0.6 (atropine) vs 1.8 +/- 0.2 mm (control), both P < 0.05 between groups]. In contrast, in the dysfunction group the overall effect of atropine was less pronounced. CONCLUSION: In patients with normal left ventricular function atropine improves coronary flow and reduces myocardial lactate production and ST-segment depression during atrial pacing, suggesting a reduction in myocardial ischaemia.     

Evaluation of coronary reserve in angina pectoris with angiographically normal coronary arteries

Coronary reserve was studied: 1) during rapid atrial pacing and then, 2) during dipyridamole infusion (0.6 mg/Kg/4 min) in 3 groups of subjects: 13 patients with angina pectoris and angiographically normal coronary arteries (ANC) with proven myocardial ischaemia during atrial pacing, 15 patients with coronary artery disease (COR) and 17 normal controls with normal coronary angiography and atrial pacing. Coronary sinus flow (QCS) was measured by thermodilution and myocardial metabolism studied by the coefficient of lactate extraction (K). At maximal pacing rates, K remained 15 p. 100 in the control group (average 24 +/- 7 p. 100) but was inversed in the ANC (-3 +/- 10 p. 100) and COR groups (-27 +/- 38 p. 100). The risk in QCS was low in the COR group (+60 +/- 33 p. 100) p less than 0.02, but significant in the ANC group (+104 +/- 57 p. 100) and normal controls (+107 +/- 41 p. 100). Coronary reserve, calculated as the percentage increase in QCS with dipryridamole, was found to be the same in the ANC group (+225 +/- 79 p. 100) as in normal subjects (+191 +/- 81 p. 100) but was low in the COR group (74 +/- 42 p. 100, p less than 0,001). Therefore, no reduction in coronary reserve was shown in patients with angina and normal coronary arteries whilst the myocardial ischaemia in coronary disease does seem to be related to an amputation of the coronary reserve.     

Intracardiac electrode detection of early ischaemia in man.

We have evaluated an intracardiac technique for the study of the electrophysiological patterns of early or subendocardial ischaemia in man. Simultaneous recordings of the paced endocardial evoked response and monophasic action potentials were obtained during pacing stress testing in 10 patients with reversible myocardial ischaemia. Early patterns of change occurred in both these recordings in response to regional ischaemia. Abnormal rate corrected shortening of the local repolarisation time in the paced endocardial evoked response from the left ventricular ischaemic zone diverging from control non-ischaemic values by a mean of 10.6% was paralleled by decreases in the simultaneous paced monophasic action potentials duration. A differential delay in the local activation time and conduction was also documented by the paced endocardial evoked response and monophasic action potential electrodes. Non-ischaemic control zones showed no changes in the pattern of activation and repolarisation. Disparate repolarisation times and asynchronous activation within the myocardium were thus consistently demonstrated during regional ischaemia. These changes in the endocardial paced evoked response and monophasic action potentials always preceded the appearance and regression of the clinical ischaemia. Intracavitary recordings may thus provide earlier and more sensitive detection of regional ischaemia during cardiac catheterisation or coronary artery surgery. The study of the patterns of activation and response could permit the assessment of interventions on the early electrical changes of ischaemia, and may bridge the gap between in vitro studies and the electrophysiological studies performed upon the intact heart.     

Improved myocardial lactate extraction after propranolol in coronary artery disease: effected by peripheral glutamate and free fatty acid metabolism.

Ten patients with chronic effort angina and coronary artery disease (luminal diameter reduction greater than 75%) were stressed by atrial pacing (140 beats/minutes) before and 15 minutes after intravenous propranolol (mean dose 7.4 mg). Myocardial substrate exchange of oxygen, blood lactate, plasma free fatty acids, citrate, glucose, glutamate, and alanine as well as coronary sinus blood flow were measured. Coronary sinus blood flow, oxygen consumption, and systemic haemodynamics did not change after propranolol. Propranolol did not influence arterial lactate concentration, and it reduced the arterial concentration of free fatty acid by 37% and increased that of glutamate by 21%. During pacing myocardial lactate extraction increased in all 10 patients; in two lactate release was converted to lactate uptake. Propranolol reduced free fatty acid uptake and increased glutamate uptake during pacing. For both substances the changes in aortocoronary sinus differences or in uptake or both correlated positively with the changes in their delivery to the heart from extracardial sources (arterial concentrations/loads). In the unstressed state before pacing, aortocoronary sinus lactate differences correlated inversely with free fatty acid differences and positively with those of glutamate. During pacing the relation between lactate and glutamate differences remained positive while the inverse correlation between lactate and free fatty acid differences was lost. Myocardial citrate release was halved during pacing and recovery. Propranolol did not influence alanine or glucose exchanges. An improved myocardial lactate extraction after propranolol administration may be secondary to decreased free fatty acid uptake or increased glutamate uptake or both. In the unstressed state both mechanisms may be of importance. During pacing induced ischaemia, increased glutamate uptake is more likely than reduced free fatty acid uptake to be the mechanism responsible for the improvement in myocardial lactate extraction. The propranolol mediated alterations in myocardial substrate exchanges may reflect the extracardial effects of the drug.     

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.     

Improved myocardial lactate extraction after propranolol in coronary artery disease: effected by peripheral glutamate and free fatty acid metabolism

Ten patients with chronic effort angina and coronary artery disease (luminal diameter reduction greater than 75%) were stressed by atrial pacing (140 beats/minutes) before and 15 minutes after intravenous propranolol (mean dose 7.4 mg). Myocardial substrate exchange of oxygen, blood lactate, plasma free fatty acids, citrate, glucose, glutamate, and alanine as well as coronary sinus blood flow were measured. Coronary sinus blood flow, oxygen consumption, and systemic haemodynamics did not change after propranolol. Propranolol did not influence arterial lactate concentration, and it reduced the arterial concentration of free fatty acid by 37% and increased that of glutamate by 21%. During pacing myocardial lactate extraction increased in all 10 patients; in two lactate release was converted to lactate uptake. Propranolol reduced free fatty acid uptake and increased glutamate uptake during pacing. For both substances the changes in aortocoronary sinus differences or in uptake or both correlated positively with the changes in their delivery to the heart from extracardial sources (arterial concentrations/loads). In the unstressed state before pacing, aortocoronary sinus lactate differences correlated inversely with free fatty acid differences and positively with those of glutamate. During pacing the relation between lactate and glutamate differences remained positive while the inverse correlation between lactate and free fatty acid differences was lost. Myocardial citrate release was halved during pacing and recovery. Propranolol did not influence alanine or glucose exchanges. An improved myocardial lactate extraction after propranolol administration may be secondary to decreased free fatty acid uptake or increased glutamate uptake or both. In the unstressed state both mechanisms may be of importance. During pacing induced ischaemia, increased glutamate uptake is more likely than reduced free fatty acid uptake to be the mechanism responsible for the improvement in myocardial lactate extraction. The propranolol mediated alterations in myocardial substrate exchanges may reflect the extracardial effects of the drug.     

Acute myocardial ischaemia induces cardiac carnitine release in man

In animal studies, prolonged periods of ischaemia decrease thecardiac carnitine content. However, whether in humans the heartloses carnitine during short-term ischaemia, and whether thisis related to ischaemia-induced cardiac dysfunction, is as yetunknown. Carnitine kinetics were investigated in 28 normotensivepatients with significant left coronary artery disease, duringand after incremental atrial pacing. To evaluate carnitine kineticsfrom the ischaemic area, patients were grouped as those with(n=22) or without (n=6) myocardial lactate production. Atrialpacing resulted in a comparable maximal heart rate and ST depressionin both groups. Carnitine kinetics did not change in those withoutlactate production. In contrast, coronary venous free carnitinelevels increased significantly by 9% during pacing in thosewith lactate production. Cardiac free carnitine balance changedfrom uptake (255 ± 107 pmol. min^–1, mean ±SEM) to release (–150 ± 66 pmol. min^–1) at30 min after pacing in the group with lactate production. Arterialand coronary venous differences in free carnitine were significantlycorrelated with myocardial lactate extraction immediately afterpacing. The change in coronary venous free carnitine was significantlycorrelated with the change in left ventricular ejection fractionat 10 min after pacing. Thus, in patients with coronary arterydisease, short-term mild myocardial ischaemia results in significantcardiac free carnitine loss.     

Lack of ouabain effect on pacing-induced myocardial ischemia in patients with coronary artery disease

Sixteen patients with significant two and three vessel coronary artery disease but without clinical congestive heart failure were studied during rapid atrial pacing before and after infusion of 0.015 mg/kg of ouabain. Seven patients with a decreased (less than 50 percent) election fraction and nine patients with a normal election fraction had a significant (P < 0.05) increase in resting arterial systolic pressure after the administration of ouabain. However, resting values for coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and myocardial lactate extraction did not change significantly in either group. During pacing, patients with a decreased ejection fraction demonstrated more ischemia than patients with a normal ejection fraction; however, the administration of ouabain did not significantly alter pacing-related changes in coronary sinus flow, myocardial oxygen consumption, myocardial lactate extraction, ischemic electrocardiographic changes or onset of chest pain in either group. The administration of ouabain has a negligible effect on coronary hemodynamics, myocardial metabolism or clinical signs of ischemia in patients with coronary artery disease with normal or abnormal left ventricular function.     

Myocardial bridging and milking effect of the left anterior descending coronary artery: Normal variant or obstruction?

Of 5,250 patients undergoing coronary arteriography over a 5 year period, 27 (0.51 percent) had an intramyocardial segment of the left anterior descending coronary artery producing a milking effect or constriction of the artery during systole. Of these, 11 patients with otherwise normal coronary arteries were studied. Hemodynamic data, coronary sinus blood flow and myocardial lactate extraction were measured during atrial pacing at rates of 120 and 150 beats/min and during a 60 watt supine ergocycle exercise test. The degree of narrowing of the left anterior descending coronary artery during systole was graded 3 (greater than 75 percent), 5 patients; 2 (50 to 75 percent), 4 patients; and 1 (less than 50 percent), 2 patients. Four patients with a grade 3 milking effect had S-T depression in the electrocardiogram indicating anterior wall ischemia and lactate production during pacing at 149 ± 2 (mean ± standard error of the mean) beats/min. Three patients had severe angina during pacing. Two patients with a grade 2 milking effect had angina-like chest pain and electrocardiographic changes during pacing at 150 beats/min. However, lactate extraction was unchanged during pacing. Two patients with a grade 1 milking effect had no angina and no electrocardiographic or metabolic abnormalities. Coronary sinus blood flow increased significantly with pacing and ergocycle exercise in all patients (rest 118 ± 8 ml/min; pacing at 150 beats/min 219 ± 27 ml/min; ergocycle exercise 251 ± 17 ml/min) (P < 0.001). We conclude that a grade 3 milking effect observed at coronary arteriography can result in significant obstruction of the left anterior descending coronary artery with typical angina and anterior wall ischemia during tachycardia. Surgical periarterial muscle resection or bypass of the left anterior descending coronary artery might be considered in symptomatic patients with this rare anomaly.     

Clinical significance of myoglobin and troponin-T in short-lasting severe myocardial ischemia

BACKGROUND: Myoglobin, cardiac troponin-T and creatine phosphokinase are biochemical indicators of acute coronary syndromes, however, the clinical significance in myocardial ischemia is not well established. Our aim was to elucidate their release kinetics in a well-defined short-lasting myocardial ischemia. METHODS: A coronary sinus lactate study with incremental atrial pacing was performed in 27 patients with significant coronary stenosis. Troponin-T, myoglobin and creatine phosphokinase samples were withdrawn from the coronary sinus and a peripheral vein before, 1, 5, 10, 30, 45 min and 1, 2, 3, 6, 12 h after pacing. RESULTS: Pacing stress induced a severe myocardial ischemia with a duration of 5.8+/-1.6 min, angina pectoris in 22/27, significant ST-segment depressions in 25/27 patients (0.34+/-0.11 mV) and a frank cardiac lactate production of 37.6+/-19.9%. Serum troponin-T levels as well as creatine phosphokinase were normal at baseline and remained unchanged. A transient rise of myoglobin after 1 h with a peak coronary sinus concentration after 2 h (101.5+/-39.0 microg/l) and peripheral venous concentration (90.5+/-32.5 microg/l) after 3 h (134.3% and 120.7%, respectively, of the upper normal limit, p<0.002) followed myocardial ischemia. In a control group of 20 patients without heart disease all variables remained unchanged. CONCLUSIONS: Severe short-lasting myocardial ischemia did not enhance troponin-T or creatine phoshokinase concentrations, whereas a transient slight cardiac release of myoglobin with a delay of 1 h and a coronary sinus peak concentration after 2 h was detected. This may be due to a rapid reperfusion effect on ischemic myocardium or minor damaged single myocardial cells.     

Short-term myocardial uptake of lidocaine and mexiletine in patients with ischemic heart disease

Determination of short-term myocardial drug uptake and subsequent redistribution was performed in 27 patients with ischemic heart disease for the antiarrhythmic agents lidocaine and mexiletine, using frequent simultaneous measurements of drug concentration in aortic and coronary sinus blood, combined with measurement of coronary sinus blood flow after intravenous bolus injection of the drug. Maximal myocardial drug content per unit resting coronary sinus blood flow (MDC:F) was significantly greater in patients in whom coronary sinus pacing at 100 beat/min was performed during the initial period of drug uptake. Maximal myocardial drug content occurred after 2.4 +/- 0.2 (SEM) for lidocaine and after 5.5 +/- 0.6 min for mexiletine (p less than .001), and pacing did not affect time to maximum myocardial drug content. In nonpaced, but not paced, patients maximal MDC:F was greater in the lidocaine group than that in the mexiletine group. The subsequent efflux of lidocaine from the myocardium was more rapid that that of mexiletine in both paced and nonpaced groups.     

Abnormalities in myocardial perfusion during tachycardia in dogs with left ventricular hypertrophy: metabolic evidence for myocardial ischemia

This study tested the hypothesis that in the chronically hypertrophied left ventricle pacing stress may cause abnormalities of perfusion that result in myocardial ischemia. Left ventricular hypertrophy (LVH) was produced by banding the ascending aorta of 10 dogs at 6 weeks of age, and studies were carried out after the animals had reached adulthood and when mean left ventricular/body weight ratio was 74% greater than in eight control dogs. Myocardial blood flow was measured with microspheres during pacing at 100, 200, and 250 beats/min, while aortic and coronary sinus blood samples were obtained for determination of concentrations of lactate and the adenosine metabolites inosine and hypoxanthine. In the control dogs, increasing heart rates were associated with an increase in mean myocardial blood flow while subendocardial flow was maintained at a level equal to or greater than subepicardial flow. Myocardial lactate uptake ranged from +60% to -5%, and adenosine metabolites were not detected in coronary sinus blood (less than 0.5 microM/l). In four dogs that underwent aortic banding no production of lactate or adenosine metabolites was observed at any heart rate; in these animals subendocardial flow was maintained at a level equal to or greater than subepicardial flow at all pacing rates. The remaining six dogs with LVH demonstrated net lactate production significantly greater than control during pacing at 250 beats/min; five of these six animals also produced adenosine metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)