External counterpulsation: Coronary hemodynamics and use in treatment of patients with stable angina pectoris

External pressure counterpulsation (ECP) has been reported to improve the clinical status of patients with angina pectoris. To document the mechanisms for such an improvement left ventricular oxygen consumption and lactate metabolism, coronary sinus blood flow, and cardiac index were studied in 10 patients with angina pectoris 1) prior to and during ECP; and 2) during right atrial pacing before and after 4 consecutive 2-hour sessions of ECP treatment. During ECP peak early and mean arterial diastolic pressures were significantly raised above control values by 32 and 13% respectively. However, coronary sinus blood flow, left ventricular oxygen consumption and left ventricular lactate extraction, mean systolic arterial pressure and cardiac index were not significantly altered by ECP. Right atrial pacing at 140 beats/min increased coronary sinus blood flow 70% over control values and induced angina and ischemic ST segment changes in 8 patients before and after 4 consecutive treatments of ECP. ECP treatment did not significantly modify the above metabolic and hemodynamic responses at rest or during atrial pacing. Although 5 patients reported improvement in angina symptoms the effect was transitory. No significant improvement over pre ECP-treatment exercise angina threshold was observed immediately following or at 1 and 3 months post treatment. This method of noninvasive circulatory assistance appears to be of doubtful value in the management of patients with stable angina pectoris.     

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 < 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<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 < 0.05) and decreased the left ventricular time constant T(26.4 ± 3.6 msec to 20.2 ± 2.4, p < 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.     

Coronary heart disease. Differential hemodynamic, metabolic, and electrocardiographic effects in subjects with and without angina pectoris during atrial pacing

Right atrial pacing was performed in 41 subjects with coronary heart disease. Twenty developed angina pectoris during pacing, while 21 did not. The extent of coronary artery disease, as judged by selective cinearteriography, was similar in the two groups. Both had significant increases in heart rate and pressure-time per minute, but there was no significant difference in either of these parameters between groups. Among the hemodynamic parameters measured, the only statistically significant change was in the cardiac index which fell slightly but significantly in the angina group. There were no differences in myocardial oxygen extraction either within each group or between groups. In the angina group, however, 14 of 20 subjects exhibited abnormal myocardial lactate metabolism during pacing. The mean change was highly significant (P < 0.01). In the nonangina group, eight of 21 subjects had abnormal lactate metabolism during pacing and the mean change was significant (P < 0.05). There was no correlation between abnormal lactate metabolism and electrocardiographic evidence of myocardial ischemia in either group. Sublingual nitroglycerin, given to five subjects with angina while pacing was continued, resulted in prompt relief of symptoms, but abnormal lactate metabolism and ST-segment depression were unaffected after 10 min. By contrast, when anginal symptoms were relieved in five subjects by cessation of pacing, symptomatic improvement was accompanied by marked improvement in lactate metabolism after 10 min. Although angina pectoris appears to be related statistically to subnormal left ventricular function and abnormal lactate metabolism, there is significant individual variation.     

Effect of aortocoronary bypass surgery on coronary circulation and myocardial metabolism during atrial pacing

Summary Eleven patients with coronary heart disease, in whom at least one of several bypass grafts to the left coronary artery was patent, were selected for the study. The hemodynamics, coronary sinus blood flow, myocardial oxygen consumption, and myocardial lactate metabolism were evaluated at rest and during atrial pacing stress test before and after surgery.There were no significant improvements in the cardiac index, pulmonary arterial end-diastolic pressure, and left ventricular ejection fraction after aortocoronary bypass surgery. However, significant improvement of coronary sinus blood flow, myocardial oxygen consumption, and myocardial lactate extraction and consumption were found during postoperative atrial pacing compared with the preoperative findings.These results suggest that successful bypass grafting may improve myocardial lactate metabolism in ischemic lesions and contribute to the postoperative relief of angina.     

Haemodynamic and metabolic effects of atenolol in patients with angina pectoris.

Myocardial substrate extraction, coronary sinus flow, left ventricular pressure, and cardiac output were measured in 11 patients with angina pectoris at three pacing rates before and after atenolol (0.2 mg/kg). Left ventricular pressures, and the product of systolic pressure time index and heart rate did not change, but max dP/dt and KV max fell after atenolol. Only at the lowest pacing rate did the drug reduce cardiac output. Coronary sinus blood flow and myocardial oxygen uptake did not change after atenolol. At the highest pacing rate before atenolol four patients developed angina, accompanied by a rise in end-diastolic pressure. After atenolol angina was abolished in three, but the end-diastolic pressure still rose at the highest pacing rate. Myocardial lactate extraction ratio fell as heart rate increased, and was lower in the patients who developed angina. After atenolol, lactate extraction ratio increased significantly at the highest and lowest pacing rates. Myocardial pyruvate extraction rose after the drug. Arterial concentrations of hydroxybutyrate and acetoacetate fell after atenolol, but the decrease in their extraction was not significant. Myocardial extraction of free fatty acids was related to arterial concentration, which fell after atenolol. The changes in lactate and pyruvate extraction after atenolol were related inversely to changes in arterial free fatty acid concentration suggesting that the improvement in myocardial metabolism could have been secondary to reduced peripheral lipolysis. The increase in lactate extraction was associated with relief of angina, but did not abolish the rise in end-diastolic pressure induced by pacing.     

Haemodynamics and myocardial metabolism in patients with obliterative coronary arteriosclerosis and tachycardia induced by pacing.

Fifty-three men with significant obliterative arteriosclerosis of coronary arteries were examined at rest, during and after pacing. Pacing induced both angina pectoris and depression of the ST segment in 38% of the patients; either angina pectoris or depression of ST segment, in 32% of the patients; the remaining 30% of patients were without symptoms or ECG signs of coronary insufficiency. Haemodynamic findings at rest, or during and after cessation of pacing were not different between these groups. Pacing increased heart rate, cardiac index remained unchanged, the stroke volume decreased, the left ventricular ejection time shortened. In both systemic and pulmonary arteries the systolic pressures decreased, the diastolic and mean pressures rose. The left ventricular end-diastolic pressure decreased. In 28 of the patients the myocardial metabolism was investigated. A close correlation was found between positive symptoms and ECG signs of myocardial ischaemia on the one hand, and metabolic signs on the other hand. Absence of angina pectoris and depressions of the ST segment during pacing does not exclude the presence of metabolic signs of ischaemia; an opposite finding is about three times less frequent. The study offers objective information about haemodynamics and myocardial metabolism before, during and after pacing, and represents an attempt of a simple classification of symptoms and signs of induced ischaemia.     

The protective effect of glucose-insulin-potassium on the response to atrial pacing.

The effects of glucose-insulin-potassium infusion (GIK) on atrial pacing-induced angina, ST depression, abnormal left ventricular end-diastolic pressure during pacing interruption (LVEDPi) and lactate metabolism (L), were studied in 18 patients: ten had angina during pacing = Ischemic group, and eight (5 normals and 3 with coronary artery disease) remained asymptomatic = Nonischemic group. The study consisted of 8-10 minute periods of control, pacing and recovery, before and after GIK. No untoward effects were observed. Comparison of the pacing responses (GIK vs pre-GIK states) showed that during GIK, angina occurred in only 4 patients, while significantly less severe changes were observed in ST depression (1.4 +/-0.5 vs 2.4 +/- 0.4 mm) and LVEDPi (16 +/- 3 vs 23 +/- 3 mm Hg). Lactate extraction was also higher (8.1 +/- 10.9 vs -5.2 +/- 11.1%), but not significantly so, although L became normal in 4 subjects and improved in another. These results indicate that GIK infusion was well tolerated and had a beneficial effect on pacing-induced myocardial ischemia.     

Angina pectoris with angiographically normal coronary arteries: a clinical, hemodynamic, and metabolic study

Seventy-six patients with anginalike chest pain (ALCP) and angiographically normal coronary arteries (NCA) had a study of the myocardial metabolism at rest and during maximal atrial pacing. The results were compared with pain characteristics, electrocardiogram, left ventricular, and coronary hemodynamic data. Coronary blood flow (CBF) was measured by continuous thermodilution. At maximal paced heart rate, the study of the myocardial metabolism distinguished two groups: (1) a first group of 50 patients whose lactate extraction coefficient was equal to or exceeded 9% and was considered as normal (Gr. I, K greater than or equal to 9%); (2) a second group of 26 patients whose lactate extraction coefficient was below 9% (Gr. II, K less than 9%), significant of myocardial ischemia. In group I (K greater than or equal to 9%), chest pain was usually atypical (typical in only 25% of cases) and rapid atrial pacing most often caused neither pain nor ECG changes. The hemodynamic and angiographic study showed minor alterations of the left ventricular cavity in 50% of cases. In group II (K less than 9%), chest pain was typical in 50% of the patients and maximal atrial pacing most often caused chest pain (85%) and ST-segment depression (80%). In almost every case, the left ventricular and the coronary angiograms were normal. Only in this group, which had clinical, electrical, and metabolic signs of myocardial ischemia, could the diagnosis of angina pectoris with angiographically normal coronary arteries be upheld.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical, hemodynamic and metabolic responses during pacing in the supine and sitting postures in patients with angina pectoris.

Hemodynamics during sinus rhythm and pacing-induced angina were studied in the supine and sitting positions in 12 patients with coronary artery disease. During sinus rhythm, left ventricular end-diastolic pressure, cardiac index, stroke index and left ventricular stroke work index were lower and heart rate was higher in the sitting position. During pacing, left ventricular end-diastolic pressure, stroke index and left ventricular stroke work index decreased, whereas pulmonary arterial mean pressure, mean pulmonary capillary wedge pressure and brachial arterial systolic and mean pressure remained unchanged in both positions. During pacing, angina was experienced by 12 patients in the supine and 10 patients in the sitting position. Chest pain was less severe and the pacing rates required to induce angina were higher in the sitting position (159 ± 3versus 132 ± 4 beats/min, P < 0.001). Comparison of data during pacing revealed lower values for left ventricular end-diastolic pressure, cardiac index, stroke index and left ventricular stroke work index, and higher values for heart rate and rate-pressure product in the sitting position; brachial arterial systolic and diastolic pressure, pulmonary arterial mean pressure and mean pulmonary capillary wedge pressure were similar in the two positions. In the immediate postpacing period, left ventricular end-diastolic pressure was lower in the sitting than in the supine position. Although the pacing threshold for angina was higher and the left ventricular end-diastolic pressure lower in the sitting position, myocardial lactate uptake was more often abnormal in this posture.     

Myocardial metabolism of glutamate and left ventricular function in patients with coronary arterial disease

Fractional myocardial extraction of glutamate, glutamine, ammonia, glucose and lactate was studied in 35 male patients during rest and atrial pacing. Fourteen patients had no coronary arterial disease. In 21 patients with coronary arterial disease and left ventricular dysfunction the increased myocardial extraction of glutamate at rest positively correlated with increased extraction of glucose, lactate and glutamine release, while it was inversely related to ammonia release. In 9 of these 21 patients pacing did not affect either left ventricular contractile function or myocardial metabolism of all studied compounds. In the other 12 patients pacing caused a decrease in left ventricular ejection fraction, velocity of circumferential fiber shortening and new regional wall motion abnormalities. A more pronounced pacing-induced left ventricular dysfunction was accompanied by myocardial lactate production and 2-fold decrease in myocardial glutamate extraction which was associated with the reduction of glutamine release and increased myocardial ammonia production. Possible relationships between alterations in myocardial glutamate metabolism and diminished ventricular performance have been reviewed. The results suggest the importance of myocardial glutamate extraction for the contractile function of human ischemic heart.     

Effects of diltiazem during tachycardia-induced angina pectoris

To investigate the mechanism of relief of angina pectoris by diltiazem administration, 14 patients with effort angina were studied using a protocol to control heart rate. Coronary, systemic and left ventricular (LV) hemodynamic function was assessed at rest and during tachycardia stress (atrial pacing)-induced angina before and during diltiazem infusion. Angina occurred in all patients during tachycardia stress before diltiazem administration. During tachycardia stress at the heart rate that produced angina after diltiazem infusion, pressure-rate product, coronary sinus flow and resistance and ST-segment depression were all similar to findings before diltiazem. Although at the onset of angina, systolic pressure was usually slightly lower after diltiazem infusion (138 +/- 11 vs 128 +/- 11 mm Hg, p less than 0.05), the pacing rate at onset of angina was higher in only 3 patients and the pressure-rate product was higher in only 1 patient. After diltiazem, left ventricular end-diastolic pressure increased less frequently after interruption of pacing. The results suggest that diltiazem favorably alters the relation between myocardial oxygen demand and supply at rest, but during tachycardia, anginal threshold and coronary reserve do not change. Diltiazem's potent antianginal action, shown in previous investigations using exercise-induced angina, is not prominent when heart rate is controlled. The major benefit of diltiazem in patients with stress-induced angina is related to reduction of myocardial oxygen demand rather than improved myocardial oxygen delivery.     

Effect of digoxin on coronary blood flow and myocardial oxygen consumption in patients with chronic coronary artery disease

In 10 patients with chronic coronary artery disease and without clinical evidence of congestive heart failure, the effects of 1.0 mg of digoxin intravenously on systemic hemodynamics, coronary blood flow, myocardial oxygen consumption and myocardial lactate extraction were studied both at rest and during atrial pacing. Atrial stimulation at a rate just below the threshold for angina led to a significant decrease in left ventricular enddiastolic pressure, from 10.6 ± 1.6 to 7.1 ± 0.8 mm Hg, associated with a significant decrease in left ventricular stroke work index per beat, from 76.7 ± 5.11 to 40.3 ± 4.01 g-m/m². After digoxin, nearly identical results in stroke work index could be observed at rest and during stimulation (75.2 ± 6.74 and 44.1 ± 5.92, respectively). However, left ventricular enddiastolic pressure decreased significantly before and during atrial stimulation (8.1 ± 1.29 and 4.7 ± 1.09 mm Hg, respectively). Cardiac index decreased from 3.08 ± 0.20 to 2.73 ±0.17 liters/min per m² at rest but during pacing it no longer differed before and after digoxin (3.17 ± 0.22 and 3.10 ± 0.20 liters/min per m², respectively). Myocardial oxygen consumption and lactate extraction remained unchanged after digoxin both at rest and during atrial pacing.It is concluded that some deficiency in left ventricular function is present in patients with chronic coronary artery disease even without clinical evidence of congestive heart failure. Digoxin improves left ventricular performance at rest and during stress conditions. An expected increase in myocardial oxygen consumption due to enhanced contractility is completely counterbalanced, probably by a decrease in left ventricular volume after digoxin.     

Antianginal and cardiac metabolic effects of low-dose glucose infusion during pacing in patients with and without coronary artery disease

Anginal threshold and cardiac metabolism during infusion of glucose, 350 mg/min, were compared with control values before, during, and after pacing in nine patients with coronary artery disease (CAD) and nine patients without coronary artery disease (non-CAD). Pacing induced no ischemia in non-CAD patients; in CAD patients, intolerable angina developed in less than 5 minutes. However, glucose infusion in the latter group increased the time to onset of angina (110 +/- 24 seconds before infusion versus 140 +/- 24 seconds following infusion) and decreased the extent of ST segment depression (1.8 +/- 0.3 mm before infusion versus 0.9 +/- 0.2 mm following infusion, p less than 0.01) following pacing. In all subjects, arterial levels and cardiac uptake of glucose rose by 100% (p less than 0.001) and those of free fatty acids fell by 50% (p less than 0.01). Arterial lactate and uptake of lactate by nonischemic myocardium increased by 30% (p less than 0.05). During pacing in CAD patients, this elevated uptake was outweighed by similar increases of lactate release from ischemic areas, leaving mean negative global exchanges unaltered. In CAD patients solely, rebuilding of cardiac glycogen after pacing was suggested from augmented citrate efflux in the control period but not during glucose infusion, suggesting a glycogen-sparing effect. Arterial concentrations and net cardiac fluxes of oxygen, glutamate, and alanine remained unaltered. In conclusion, beneficial effects of glucose during ischemia are associated with increased aerobic and anaerobic glycolysis, saving of glycogen, and decreased lipolysis.     

The effects of trapidil on left ventricular function and platelet aggregation in patients with coronary artery disease subjected to pacing.

The effects of the intravenous administration of 100 mg of trapidil on systolic and diastolic left ventricular functions and coronary sinus blood flow, as well as on myocardial lactate metabolism and platelet aggregation, were investigated before and after pacing in 12 patients with coronary artery disease. Pacing without administration of trapidil provoked angina in 6 of these patients. During rest, trapidil decreased the mean blood pressure by an average of 5 mmHg (from 112 +/- 15 to 107 +/- 8 mmHg, p less than 0.05) and the left ventricular end-diastolic pressure by an average of 4 mmHg (from 10 +/- 3 to 6 +/- 2 mmHg, p less than 0.05). Trapidil also caused both the max dp/dt and the coronary sinus blood flow to increase slightly, although it had no significant effect on diastolic function, myocardial lactate metabolism, or platelet aggregation. During the pacing that followed trapidil administration, chest pain was not provoked in the same 6 patients who had previously experienced chest pain on pacing. The extent of ST-segment depression also improved from -1.6 +/- 0.3 to -0.9 +/- 0.7 mm (p less than 0.05) and there was a significant suppression of the production of myocardial lactate. When pacing was terminated, trapidil caused a decrease in left ventricular systolic pressure from 173 to 156 mmHg (p less than 0.05), and also caused a decrease of the left ventricular end-diastolic pressure, from 16 +/- 4 to 8 +/- 2 mmHg (p less than 0.05). Trapidil had no significant effect on platelet aggregation activity with either a 1 microM or a 2 microM dose of ADP (adenosine diphosphate). However, the beta-TG level was suppressed, decreasing from 119 +/- 14 to 99 +/- 19 ng/ml in the arterial blood (p less than 0.1) and from 114 +/- 9 to 103 +/- 17 ng/ml (p less than 0.1) in the coronary sinus blood. Reductions in the preload and afterload by trapidil were of far greater magnitude than either its coronary dilatory or positive chronotropic effects in patients with coronary artery disease. Thus trapidil, a new antianginal agent appears to inhibit the production of platelet derived growth factors and may, therefore, protect the arteries from atherosclerosis as it promotes beneficial systemic hemodynamics in patients with depressed ventricular function.     

Effect of timolol maleate on pacing induced myocardial ischaemia.

The effects of timolol maleate administered intravenously on coronary and systemic haemodynamics, myocardial metabolism, and plasma catecholamine concentrations were assessed in 10 patients with confirmed coronary artery disease. Rapid atrial pacing to the onset of angina was performed in all patients. Timolol reduced cardiac output at rest and during pacing and reduced resting heart rate but did not affect arterial blood pressure. Left ventricular stroke work index fell during pacing. Coronary sinus blood flow was unchanged, but pulmonary artery diastolic pressure rose after timolol. The drug produced clinical improvement in nine of the 10 patients with prolongation of the mean pacing time to angina. There was evidence of improved myocardial metabolism with a change from production to extraction of lactate: Arterial noradrenaline concentrations at rest rose after timolol. In these patients with coronary artery disease timolol produced an increased tolerance to atrial pacing stress, which appears to be due to a combination of effects including reduced myocardial contractility and decreased lipolysis.     

Beta-adrenergic stimulation with isoproterenol enhances left ventricular diastolic performance in hypertrophic cardiomyopathy despite potentiation of myocardial ischemia. Comparison to rapid atrial pacing

Impaired left ventricular relaxation and filling is an important pathophysiologic mechanism in hypertrophic cardiomyopathy. To determine whether isoproterenol, known to improve relaxation in isolated cardiac muscle, could favorably modify this effect, we assessed simultaneous left ventricular volume and regional systolic asynchrony (by radionuclide angiography), left ventricular pressure (by micromanometer catheters), and lactate metabolism in 12 patients with hypertrophic cardiomyopathy. Pressure-volume relations were studied during atrial pacing stress to induce myocardial ischemia and during isoproterenol infusion to similar heart rates. Angina occurred in 10 patients with pacing and in 11 patients during isoproterenol infusion; lactate consumption was reduced in nine patients during isoproterenol compared with pacing, including five patients who produced lactate with isoproterenol. During isoproterenol compared with pacing, peak left ventricular pressure was higher (205 +/- 33 vs. 142 +/- 21 mm Hg, p less than 0.001), ejection fraction was higher (77 +/- 10% vs. 71 +/- 12%, p less than 0.02), and regional systolic nonuniformity was diminished. Despite ischemia, these changes in load and nonuniformity during isoproterenol were associated with enhanced diastolic function compared with pacing tachycardia: isoproterenol reduced T 1/2, the half-time of pressure decline after peak negative dP/dt (from 46 +/- 10 to 33 +/- 6 msec, p less than 0.001), shifted the diastolic pressure-volume curve downward and rightward in 10 of 12 patients, and increased end-diastolic volume (from 77 +/- 18% to 100 +/- 11% of control values, p less than 0.001) with no change in end-diastolic pressure (19 +/- 7 to 19 +/- 5 mm Hg, p = NS). Thus, despite ischemia, isoproterenol improved left ventricular relaxation and filling compared with tachycardia in the absence of beta-adrenergic stimulation. Although isoproterenol is detrimental in hypertrophic cardiomyopathy by provoking ischemia, these data suggest that the adverse effects of ischemia on ventricular relaxation and distensibility may be alleviated by beta-adrenergic stimulation, possibly as a result of enhanced inactivation and restored load sensitivity.     

Coronary hemodynamics and myocardial metabolism in patients with syndrome X: response to pacing stress

Coronary hemodynamics, myocardial metabolism and left ventricular function at rest and after incremental atrial pacing were evaluated in 12 patients with stress-induced angina and ST segment depression, angiographically normal coronary arteries and no evidence of spasm, generally labeled as syndrome X, and in 10 normal subjects. At baseline study, great cardiac vein flow was comparable in patients and control subjects. During pacing, an equivalent rate-pressure product was reached in the two groups, but the slope of the relation between rate-pressure product and great cardiac vein flow was significantly less steep in patients than in normal subjects (0.0027 vs. 0.0054 ml/mm Hg.beat, p less than 0.001). Nevertheless, the left ventricular ejection fraction was comparable in both groups at rest (66 +/- 6% vs. 71 +/- 7%, p = NS) and during pacing (71 +/- 7% vs. 66 +/- 5%, p = NS). At baseline study, myocardial glucose extraction was more efficient in patients with syndrome X (p less than 0.05), but net myocardial exchange of pyruvate and alanine was, respectively, smaller and greater than in control subjects. Lactate was extracted to a similar extent in the two groups and in no instance was net lactate release observed during pacing or recovery. During pacing and recovery, patients with syndrome X showed net pyruvate release, unlike the control subjects in whom net pyruvate exchange was positive. In addition, patients with syndrome X continued to show net myocardial extraction of alanine during spacing and recovery, whereas normal subjects produced alanine throughout the study. Myocardial carbohydrate oxidation increased significantly during maximal pacing in normal subjects but not in patients, in whom it always remained below (p less than 0.01) the concurrent rate of myocardial uptake of carbohydrate equivalents (glucose, lactate, pyruvate, alanine). Myocardial energy expenditure was significantly lower in patients than in control subjects at maximal rate-pressure product levels (p less than 0.01). The metabolic pattern in patients with syndrome X therefore is not consistent with classic ischemia, although differences in the net exchange of circulating substrates (glucose, pyruvate, alanine) can be demonstrated. Thus, in patients with syndrome X, the symptoms, electrocardiographic signs and impairment in the increase in great cardiac vein flow during pacing coexist with preserved global and regional left ventricular function and myocardial energy efficiency.     

Left main coronary artery disease Clinical, arteriographic and hemodynamic appraisal

Thirty patients with 70 percent or greater obstruction in the left main coronary artery were evaluated during hemodynamic and angiographic studies. There were 25 male and 5 female patients; the average age was 54 years. Twenty-seven patients had moderate to severe angina pectoris, with 14 noting an increase in severity of chest pain within 6 months before arteriography. Six patients also had hemodynamic evaluation by atrial pacing. In each, angina pectoris was easily induced, and all 6 had abnormal pacing ventricular function curves with marked increase in left ventricular end-diastolic pressure associated with a reduction in left ventricular stroke work.

Image intensification fluoroscopy revealed calcification in the left main coronary artery in 7 patients. A striking finding was the severity of obstructive disease in the other coronary arteries. Eight patients had total occlusion of the right coronary artery, and 29 of the 30 patients had 2- or 3-vessel disease. Significant coronary arterial collateral vessels were noted in 21 patients. Contraction abnormalities were present in 24 left ventriculograms.

Three deaths were associated with cardiac catheterization (mortality rate 10 percent). Only 2 of 18 patients who underwent aortocoronary bypass surgery died. The 16 surgical survivors are in clinically improved condition after a follow-up period of 10 months. Three of 9 patients not operated on have died, all within 1 month of arteriography.

Because of the high risk of sudden death, coronary arteriography should be performed with caution in a patient with severe angina pectoris, very positive findings on exercise testing, easily induced angina and heart failure with stress and calcification in the left main coronary artery. After cardiac catheterization all patients should undergo routine monitoring and, when technically feasible, saphenous vein aortocoronary bypass surgery should be performed.     

Verapamil in chronic stable angina: amelioration of pacing-induced abnormalities of left ventricular ejection fraction, regional wall motion, lactate metabolism and hemodynamics

The effects of intravenously administered verapamil (bolus dose of 0.145 mg/kg body weight, followed by continuous infusion at 0.005 mg/kg per min) on myocardial ischemia induced by incremental coronary sinus pacing were investigated in 12 patients with coronary artery disease undergoing diagnostic angiography. The effects were determined with respect to differences between changes under control pacing conditions and after verapamil in the transmyocardial gradients of lactate, systemic hemodynamics and in left ventricular ejection fraction and regional wall motion abnormalities measured with gated radionuclide ventriculography. Control and drug data could not be matched for four patients because of the development of atrioventricular (A-V) Wenckebach block at lower pacing rates during verapamil infusion. In the remaining eight patients, under control conditions, pacing to a mean maximal heart rate of 120.6 ± 10.8 beats/min produced moderate to severe chest pain in all; the left ventricular ejection fraction decreased from 0.59 ± 0.08 to 0.47 ± 0.07 (?20.2 percent, p < 0.001) with the development of new regional wall motion abnormalities in seven patients and an accentuation of the preexisting abnormality in the remainder. During verapamil administration, the left ventricular ejection fraction decreased from 0.55 ± 0.07 to 0.52 ± 0.04 (?5.5 percent, difference not significant); no regional wall motion abnormalities developed. Four patients had no chest pain; in the other four, the pain at maximal pacing was minimal or mild in intensity. Under control conditions, the maximal pacing rate led to a decrease in myocardial lactate extraction in all patients, with metabolism becoming anaerobic in four. During administration of verapamil, identical pacing rates produced no abnormalities of the transmyocardial lactate gradient while preventing the increases in pulmonary capillary wedge pressure and in pulmonary and systemic arterial pressures observed under control conditions.The overall data, demonstrating that verapamil, when given under steady state conditions of drug administration, prevents or greatly attenuates the ischemic consequences of incremental coronary sinus pacing in patients with coronary artery disease, provide objective evidence for the clinical utility of the compound in exertional angina. Controlled clinical trials during oral therapy with the drug are therefore indicated.     

Effect of surgical reduction of left ventricular outflow obstruction on hemodynamics, coronary flow, and myocardial metabolism in hypertrophic cardiomyopathy

To assess the impact of operative reduction of left ventricular outflow obstruction in hypertrophic cardiomyopathy, measurements of great cardiac vein flow, oxygen and lactate content, left ventricular pressures, and cardiac index were measured at rest and during pacing stress in 20 consecutive patients (13, myotomy-myectomy; six, mitral valve replacement; one, both myotomy-myectomy and mitral valve replacement) who underwent both preoperative and postoperative studies. All had angiographically normal epicardial coronary arteries. Operation resulted in reduction in outflow gradient (64 +/- 38 to 4 +/- 7 mm Hg, p less than 0.001) and in left ventricular systolic pressure (186 +/- 32 to 128 +/- 22 mm Hg, p less than 0.001) and was associated with reduction in great cardiac vein flow (101 +/- 26 to 78 +/- 16 ml/min, p less than 0.001) and oxygen consumption in the anterior left ventricle and septum (11.9 +/- 4.1 to 8.4 +/- 1.9 ml O2/min, p less than 0.001) in the basal state. During rapid atrial pacing, 13 of 20 patients experienced chest pain postoperatively, whereas all 20 developed chest pain during preoperative pacing, with an improvement in pacing anginal threshold (or heart rate 150 if no chest pain was experienced) of 16 +/- 18 beats/min (p less than 0.001). The peak great cardiac vein flow (161 +/- 41 to 131 +/- 45 ml/min, p less than 0.025) and myocardial oxygen consumption (19.4 +/- 6.1 to 14.3 +/- 5.5 ml O2/min, p less than 0.005) during pacing, which correlated directly with the severity of the basal left ventricular gradient (p = 0.011 and p = 0.002, respectively), were also reduced by surgery. Lactate metabolism during pacing changed from net production before surgery to net consumption after operation (-17 +/- 47.6 to 4.4 +/- 29.8 mumol/min, p less than 0.01), with six of 20 patients producing lactate after surgery compared with 13 of 20 before surgery (p = 0.06). The six patients with the highest peak great cardiac vein flow (greater than 175 ml/min) during preoperative pacing had greater symptom and metabolic benefit during pacing after surgery compared with the 14 patients with lower peak coronary flow. Postpacing left ventricular end-diastolic pressure (30 +/- 7 to 23 +/- 7 mm Hg, p less than 0.001) and pulmonary artery wedge pressure (24 +/- 6 to 20 +/- 5, p less than 0.001) were reduced after surgery.(ABSTRACT TRUNCATED AT 400 WORDS)