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Iliac-crest biopsies were obtained from 40 untreated hyperthyroid patients after double-labelling with tetracycline. Histomorphometric analyses were performed on undecalcified and decalcified bone sections. The morphometric and chemical data were compared with those in normal control groups and the results of the morphometric analyses were related to thyroid function and to chemical quantities of calcium-phosphorus metabolism. The bone turn-over was increased in the hyperthyroid patients with an increase both in bone resorption and bone formation. Serum alkaline phosphphatase was increased and positively correlated to the amount of osteoid and to the extent of tetracycline-labelled surfaces. The osteoclastic resorption was positively and the bone formation inversely correlated to thyroid activity. This might explain the reduced amount of trabecular bone found in hyperthyroidism. The most striking feature was, however, a pronounced increase in osteoclastic activity in cortical bone followed by increased porosity. The osteoclastic resorption in cortical bone was positively correlated to serum concentrations and urinary excretions of calcium and phosphorus. This indicates that increased cortical osteoclastic resorption is mainly responsible for bone mineral mobilisation in hyperthyroidism.

Myocardial exchanges of glutamate, alanine, glucose, lactate, free fatty acids (FFA) and oxygen in resting state were determined in nine subjects (controls) without and in 28 patients with coronary artery disease (CAD). Patients with CAD showed increased myocardial glutamate uptake (2.51 +/- 0.60 mumol/min) and alanine release (1.25 +/- 0.60 mumol/min) compared to controls (glutamate uptake: 1.66 +/- 0.79 mumol/min; alanine release: 0.63 +/- 0.41 mumol/min). Myocardial glucose and lactate uptake was augmented in CAD patients, whereas FFA arteriovenous differences were decreased in patients with three-vessel-disease. The amount of glutamate taken up by the heart correlated positively to lactate uptake in all subjects (r = 0.84) and to external glucose utilization in patients with CAD (r = 0.72). Myocardial alanine release was positively related to glucose and lactate uptake in controls and in patients with only moderate CAD (one-vessel-disease). Glucose and FFA uptake correlated inversely in controls (r = 0.84), but not in CAD patients. A tight relation between exchanges of glutamate/alanine and carbohydrate metabolism in human heart is demonstrated. The data suggest altered myocardial substrate exchange towards augmented carbohydrate utilization in CAD patients in resting state. The results agree with in vitro and animal studies suggesting extraction of glutamate from the circulation to be of importance for maintaining carbohydrate consumption in chronic ischaemic heart disease.

The reproducibility of coronary sinus blood flow (CSBF) (thermodilution technique) and myocardial metabolism (exchange of oxygen, lactate, free fatty acids, glucose, citrate, glutamate and alanine) during two identical pacing periods separated by 45 min were studied in eight patients with chronic coronary artery disease. The mean of the individual difference (delta-values) between values during the first (T1) and second (T2) test, at corresponding times (rest, pacing and after 3-5 min of recovery), were calculated and expressed as a percentage of the resting level of each parameter in order to assess their reproducibility. All patients experienced angina pectoris during both pacing sessions, and pacetime to onset of symptoms did not differ between the tests. Group values for haemodynamics and exchange of metabolites were acceptably reproducible throughout the period under study. Mean delta-values of CSBF ranged from 10% to 16% and myocardial oxygen uptake from 14% to 22% in relation to the resting levels. In contrast, mean delta-values of metabolites ranged from 5% to 136% in relation to the respective A-V differences during the study. The greatest variation occurred during pacing and of all the metabolites lactate exchange varied most. A spontaneous variation in the degree of ischaemia during repeat stress tests might be the major reason for the metabolite variability. Changes in CSBF, however, tended to correlate inversely to the delta-aortocoronary sinus differences of substrates during pacing. Precision of chemical analysis and blood sampling technique were of minor importance for the variability. Since lactate exchange varied most, the study suggests that additional measurements should be made of more metabolites when assessing the efficacy of therapy by means of myocardial metabolism.

Twelve patients with coronary artery stenosis (greater than 50% diameter reduction) underwent two identical periods of atrial pacing before and after i.v. verapamil (0.1 mg/kg). Myocardial exchanges of free fatty acids (FFA), citrate, lactate and glucose were evaluated from measurements of arterio-coronary sinus differences (n = 12) and coronary sinus blood flow (CSBF) (n = 9). Before verapamil 11 patients developed angina. Verapamil abolished pain in seven and improved pacing time to angina in four patients. After verapamil, aortic pressure decreased (P less than 0.05), while the rate pressure product remained unchanged during rest and pacing. Verapamil decreased CSBF by 20% (P less than 0.05) during pacing, and increased oxygen extraction both during pacing and recovery. During pacing verapamil increase net FFA extraction (P less than 0.01) and uptake (1 to 8 mumol/min P less than 0.05), and decreased glucose extraction (P less than 0.05) and uptake (22 to 11 mumol/min P less than 0.02. Verapamil increased myocardial citrate release during pacing (P less than 0.05), suggesting a citrate inhibition of glycolysis as a possible mechanism of the inhibited glucose uptake. During pacing, verapamil reduced lactate release in seven patients (P less than 0.05) and decreased lactate extraction in five patients (P less than 0.05). The results suggest that verapamil mediates its beneficial effect on pacing-induced angina, in part by changing substrate utilization of the ischaemic myocardium in man towards that of normal heart.

We studied the effects of sublingual nitroglycerin (dose range 0.5-1.0 mg) on cardiac metabolism in the resting state in 12 patients with chronic coronary artery disease. Seven patients with chronic coronary artery disease served as a control group. No patient from either of the groups experienced angina pectoris during the study. Reduced heart work after nitroglycerin was evident from a 34% decrease of oxygen uptake (P less than 0.001) and a 35% fall in coronary sinus blood flow (P less than 0.01). Nitroglycerin decreased lactate extraction by 30% (P less than 0.05), lactate uptake by 58% (P less than 0.025); glucose uptake by 47% (P less than 0.01) while net exchange of free fatty acids did not change. The aorto-coronary sinus difference of plasma citrate became increasingly negative (from -4 +/- 3 mumol/l to -8 +/- 2 mumol/l) (P less than 0.02) after nitroglycerin. In the control group coronary sinus blood flow and myocardial exchange of oxygen and substrates remained unchanged. Our results suggest a relatively increased myocardial utilization of free fatty acids compared with that of carbohydrates after nitroglycerin. This may in part be explained as an inhibition of glycolysis due to citrate accumulation. The study indicates that myocardial lipid-carbohydrate metabolism is disturbed in chronic coronary artery disease even in patients without clinical evidence of ischaemia in resting state and that nitroglycerin reverses this condition towards the metabolism of the normal heart.

During repeat exercise testing in 10 patients with stable angina, individual optimal doses of nicardipine were determined. Hemodynamic values and cardiac metabolism were studied during 2 pacing periods carried out before and after this dose (mean 5.3 mg). Postpacing ST-segment depression diminished (1 mm) after nicardipine administration (p less than 0.05), whereas pacing time to onset of angina did not change. Nicardipine administration increased heart rate 16% (p less than 0.005) and reduced systolic (10%) and diastolic (8%) blood pressures (both p less than 0.005). Coronary blood flow increased 16% (p less than 0.05) and coronary vascular resistance decreased 24% (p less than 0.01). Myocardial oxygen consumption was unchanged despite an 11% decrease in rate-pressure product during pacing (p less than 0.02). In the control state before nicardipine administration, metabolic signs of ischemia included release of lactate across the heart in 7 patients, decreased mean free fatty acid and glutamate uptake and alanine release during pacing, together with increased glucose uptake and citrate release during recovery. After nicardipine lactate release decreased in 5 of the 7 patients, pacing no longer changed free fatty acid, glutamate and alanine uptake/release from the level at rest. During recovery glucose uptake was reduced and citrate release was unaffected. The hemodynamic data indicate that nicardipine is a systemic and coronary vasodilator, increasing oxygen supply to the ischemic myocardium. The metabolic results indicate a change in substrate utilization toward that of normal heart, suggesting improved aerobic energy supply.

After 10 mg nicardipine IV a patient with stable angina developed chest pain and ST-segment depression accompanied by excessive tachycardia, low arterial blood pressure, and initially decreased coronary sinus blood flow. Measurements of arterial concentrations and cardiac exchanges of lactate, glucose, free fatty acids, glutamate, and alanine showed alterations indicative of severe ischemia.

Postabsorptive plasma concentrations of citrate, glucose, lactate, free fatty acids (FFA), ketone bodies and free insulin were measured once weekly for 5 weeks in 18 male juvenile diabetics. The circadian rhythms of the same substances were followed in 12 male diabetics. In 8 of them, daily rhythms were measured twice, before and after plasma glucose was lowered by increasing insulin doses. In the postabsorptive state, the mean plasma citrate concentration of the diabetics, 117 mumol/l (range 65--160), did not differ from that of non-diabetics despite two- to threefold higher levels of plasma glucose, FFA and ketone bodies in diabetics. Daily plasma citrate profile in diabetics showed peak concentrations in the morning and late afternoon. Citrate level throughout the day fell after increased insulin administration, whereas the diurnal pattern remained unchanged. Both the week-to-week coefficient of variation (mean 10%) and the diurnal coefficient of variation (mean 17%) of plasma citrate were below those of any other substances measured (p less than 0.001). Postabsorptive citrate concentration correlated negatively to the diurnal variation of plasma glucose whether diabetic control was apparently good or poor. The results support the idea that plasma citrate level reflects intracellular citrate regulation of glucose utilization. In spite of an interindividual range of 100%, individual citrate level was remarkably constant. Postabsorptive plasma citrate concentration is proposed as a control marker of lability of circulating glucose in insulin-treated diabetics.

Oesophageal manometry was performed in 20 patients with chest pain, of whom 10 showed coronary artery spasm (group I) and 10 did not (group II). In the basal state oesophageal spasms were recorded in 6 patients from group I but in none from group II (p less than 0.05). In group I the duration of oesophageal contractions was 4.50 +/- 0.65 s compared with 2.86 +/- 0.36 s in group II (p less than 0.05). Prolonged hyperventilation was performed during manometry by 7 patients from each group. In group I this caused chest pain in all 7, with electrocardiographic changes in 6; at the same time oesophageal spasms were intensified in 5 patients and began anew in 1. In group II no electrocardiographic changes were seen with hyperventilation, and 1 patient showed oesophageal spasm. These observations suggest a relation between spasm of the coronary arteries and spasm of the oesophagus.

Coronary sinus pacing was performed in 12 patients with and 12 patients without significant coronary artery disease as verified by angiography in order to elucidate a possible link between cardiac exchange of angiotensin-converting enzyme and the coronary circulation. The coronary sinus and arterial blood enzyme activity remained unchanged and were similar in the two groups, both at rest and during pacing, and the activity was not related to pacing-induced changes in oxygen consumption or coronary vascular resistance. Therefore it does not seem that global cardiac formation or depletion of angiotensin-converting enzyme is of regulatory importance in the coronary vascular bed in patients with and without coronary artery disease under these circumstances.

We present the case histories of two patients with angina pectoris who developed coronary artery spasm in response to provocation with prolonged hyperventilation (verified by ST segment elevation in both and coronary angiography in one) despite a negative ECG response to intravenous injection of 0.4 mg ergometrine. This new observation, which is in conflict with recent publications stating that ergot provocation is more sensitive than hyperventilation, suggests that in some patients diagnostic provocation with hyperventilation may be an alternative to the widely used ergot provocation.

Using [125I]insulin at 172 pmol/1 (1 ng/ml) the binding of insulin to mononuclear leucocytes isolated from peripheral blood was studied. Our present study comprised 21 healthy subjects (22-33 years old, 90-110% of ideal weight) and a comparable group of 22 obese subjects (20-37 years old, minimum 150% of ideal weight). A significant difference in insulin binding was found between the two groups, the mean specific insulin binding fraction in normals being 1.92 +/- 0.58 (s) X 10(-2) and that for the obese 1.19 +/- 0.41 (s) X 10(-2) (P less than 0.01). No correlation was found between body weight and the number of insulin receptors in the obese subjects. However, the number of insulin receptors was negatively correlated to fat cell size (P less than 0.05). Insulin receptors in subjects were also negatively correlated to fasting plasma insulin (P less than 0.05). Insulin receptors were studied in 11 obese subjects before and after 10 days of fasting. A significant increase in the number of insulin receptors was observed with a simultaneous decrease in plasma insulin to normal values. The results indicate that obesity complicated by hyperinsulinism is associated with a decrease in the number of insulin receptors compared with the normal. This finding may in part explain the decreased insulin sensitivity of the hyperinsulinaemic obese.

The possible relation between Na-K-pump concentration and left ventricular (LV) function was studied in 24 patients with suspected idiopathic dilated cardiomyopathy. This was done by measurement of 3H-ouabain binding to biopsies obtained during left-sided heart catheterization. In all patients light microscopy of biopsies was compatilel with dilated cardiomyopathy. Nineteen patients had impaired LV function as defined by NYHA/WHO and a Na,K-pump concentration of 331 +/- 19 pmol/g wet weight, whereas 5 patients had normal LV function and a Na,K-pump concentration of 559 +/- 62 pmol/g wet weight (p less than 0.001). The correlation between Na,K-pump concentration and ejection fraction was highly significant n = 24, r = 0.81, p less than 0.001). There was no correlation between volume fraction of collagen tissue and Na,K-pump concentration in the biopsies (n = 24, r = -0.08, p less than 0.80), indicating that the decrease in Na,K-pump concentration with dilated cardiomyopathy is not the simple outcome of increased fibrosis in the myocardium. The results indicate that the decrease in Na,K-pump concentration may be of importance for myocardial dysfunction and suggest a simple biochemical assessment of dilated cardiomyopathy by measurement of 3H-ouabain binding.

8 patients with exertional angina pectoris were treated for 3 months with a low-fat, low-calorie diet. Serum cholesterol was reduced by 28% and body-weight by 7.9 kg on average. The effect of the dietary intervention was assessed by a heart metabolic study during pacing-induced tachycardia. After dietary treatment coronary sinus blood-flow and myocardial oxygen consumption were considerably reduced, but pacing time before angina developed increased. Other improvements were a reduction in lactate release during pacing, a reduction in citrate release during recovery, a reduction in alanine output during rest and recovery, and a lower uptake of glutamate. The results suggest a beneficial effect of low-fat, low-calorie dietary treatment on myocardial energy metabolism in patients with exertional angina pectoris.

At rest, during cardiac catheterization, aortic plasma levels of immunoreactive atrial natriuretic peptide did not differ between 10 controls with atypical chest pains and normal coronary arteries and 9 patients with stable angina pectoris and coronary arterial disease (55.2 +/- 19.8 vs. 64.8 +/- 19.8 pg/ml, NS). Nor did atrial natriuretic peptide values differ between the two groups during or after atrial pacing (150 beats/minute), which induced electrocardiographic and metabolic signs of acute myocardial ischaemia in the patients with coronary arterial disease but in none of the controls. Pacing, when carried out for more than 300 seconds, induced an increase of plasma atrial natriuretic peptide that correlated with duration of pacing (r = 0.80, P less than 0.001), and similarly in controls and patients with coronary arterial disease. In a second part of the study, which included 2 controls and 2 patients with coronary arterial disease, post-pacing coronary sinus concentrations of atrial natriuretic peptide were 10-20 times higher than peripheral levels (415- greater than 890 pg/ml). The concentration of atrial natriuretic peptide rose as blood from the caval veins (34 +/- 7 pg/ml) entered the right atrium (56 +/- 24 pg/ml), but thereafter was unchanged in the pulmonary artery (51 +/- 3 pg/ml) and the aorta (46 +/- 9 pg/ml). In conclusion, the results gave no evidence for ischaemic heart disease without congestive cardiac failure to be associated with altered levels of atrial natriuretic peptide. It was confirmed that atrial pacing stimulates the secretion of atrial natriuretic peptide which is produced by the heart and released via the coronary sinus into the circulation.

Patients with typical effort angina have been considered to have normal myocardial metabolism at bodily rest (24). In contrast to this, the present study demonstrated, even in resting asymptomatic CAD patients, a decreased myocardial uptake of FFA, independent of arterial levels and probably reflecting a decreased capacity for FFA oxygenation. This was compensated for by increased aerobic, and in some cases anaerobic, carbohydrate utilization. Further more, there was increased alanine release and glutamate uptake, related to, and perhaps of importance for the maintenance of increased carbohydrate breakdown. The altered myocardial substrate preference related to the severity of ischemic disease, indicates a metabolic adaptation induced by chronic myocardial ischemia in CAD patients.

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 possible effects of lithium on myocardial morphology were studied at the light-microscopic level in three different rat models: (i) rats with chronic renal failure due to lithium administration for 8-16 weeks after birth, (ii) normal, adult rats treated with lithium for 16 weeks, and (iii) new-born rats exposed to lithium in their prenatal life. Morphological changes were found in 57% of the male rats with lithium-induced uraemia after lithium administration for 16 weeks postnatally. The changes comprised myocytic degeneration and necrosis associated with infiltration of lymphocytes, histiocytes and plasma cells. This morphological picture is different from the myocardial changes associated with chronic renal failure. Male rats with chronic uraemia after withdrawal of lithium 8 weeks postnatally showed no myocardial changes after 16 weeks. Also, male rats with normal renal function had no myocardial changes after 16 weeks on lithium, but these rats had a significantly lower plasma level of lithium than the lithium-uraemic rats (0.8 vs. 1.4 mmol/l). It is suggested that myocarditis was a consequence of persistent high plasma levels of lithium maintained in the lithium-uraemic rats and that cardiotoxic effects of lithium may be potentiated by concomitant renal failure.

Of 178 transseptal left heart catheterizations performed, 173 successful cases are reported, with the use of a Swan-Ganz, flow-directed, balloon-tipped catheter. By means of a modified Brockenbrough technique, which is described in detail, a 10F Teflon tube (3.3 mm outside diameter) was inserted into the left atrium. Through the tube, which was continuously flushed with saline solution, a 5F Swan-Ganz catheter was introduced into the left atrium. In all cases where left atrial puncture was possible (n = 173), the left ventricle was easily entered, even in the presence of mitral stenosis. Two major complications with signs of cerebral embolism occurred in this series. The method is technically reliable and acceptably safe in cases where the transseptal route of left heart catheterization is required.

In 21 control subjects with atypical chest pains and normal coronary arteries and in 64 patients with stable angina and coronary artery disease (CAD), myocardial exchanges of free fatty acids, glucose, lactate, citrate, glutamate, alanine and oxygen were determined before, during and after pacing. At rest, myocardial uptake of fatty acids was 50% lower in CAD patients than in the control subjects (p less than 0.001), whereas uptakes of glucose and lactate were twice as high (p less than 0.01). CAD patients showed increased myocardial glutamate uptake (p less than 0.001) and alanine release (p less than 0.001). In control subjects, myocardial fatty acid uptake was directly related (r = 0.54, p less than 0.01), whereas uptakes of glucose (r = -0.42, p less than 0.05) and lactate (r = -0.46, p less than 0.05) were inversely related to arterial fatty acid levels. Citrate release was inversely related to glucose uptake (R = 0.44, p less than 0.05). These relations were absent in CAD patients. Glutamate consumption correlated only with glucose uptake in CAD patients (p less than 0.001) but did so with lactate uptake and alanine release in all individuals (p less than 0.001). Pacing caused angina in the CAD patients but not in the control subjects. Pacing induced no metabolic changes among control subjects but provoked myocardial lactate release in 40 CAD patients, including an additional decrease of fatty acid uptake (p less than 0.05) and increase of glucose uptake (p less than 0.05) compared with resting levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Nine patients (mean age 32 years, range 9-58) with a secundum atrial septal defect (ASD) were investigated by intracardiac electrography before and, on an average, 14 months after circumclusion of the defect. Postoperatively, four patients developed atrial fibrillation or flutter requiring treatment. After the repair, sinus node recovery time and the H-V interval increased significantly. The P-A interval, the A-H interval, sinoatrial conduction time, and the effective refractory period of the atrium (ERPA) remained unchanged. In the patients who developed atrial tachyarrhythmias, the mean preoperative ERPA was significantly longer than in the remaining patients; in patients with ERPA less than 220 ms, no atrial arrhythmias occurred. Our findings suggest that circumclusion of a secundum ASD has a sustained deleterious effect on sinus node function and His-Purkinje conduction. Preoperative determination of ERPA might be of value for the prediction of postoperative atrial arrhythmias in patients submitted to ASD repair.

We examined the effects of antianginal drugs on myocardial uptake of glutamate and release of alanine in patients with chronic effort angina. Thirty-three patients underwent two periods of atrial pacing, the second preceded either by no medication (controls) (n = 8), 0.1 mg/kg i.v. propranolol (n = 8), 30 mg nifedipine sublingually (n = 9) or 0.75 mg glyceryl trinitrate sublingually (n = 8). Before, during, and after each pacing period, coronary sinus blood flow (CSBF), oxygen uptake, and arteriocoronary sinus differences (ACs) of plasma glutamate and alanine were determined. In all groups of patients, arterial alanine concentration fell during the second test. Except for this fall, no metabolic change was seen in controls. Propranolol increased circulating arterial concentration and ACs values of glutamate throughout the test. Nifedipine did not change arterial glutamate concentration but decreased ACs glutamate before and after pacing. Glyceryl trinitrate decreased CSBF, oxygen uptake, and net myocardial uptake of glutamate before pacing despite unchanged arterial level and ACs values. Alterations of myocardial glutamate uptake after drugs may reflect metabolic effects of propranolol primarily exerted on extracardial sites and of nifedipine exerted on the myocardium itself, whereas changes after glyceryl trinitrate seem to be secondary to its cardiac unloading effect. Alterations in myocardial release of alanine were too small and inconsistent to be taken as drug effects.

Eighteen patients, 13 male and five female, with unstable angina pectoris and who had greater than or equal to 3 anginal attacks/day despite treatment with beta- and/or Ca-blockers were treated for three days with transdermal nitroglycerin (Transiderm-Nitro 25 mg/24 hours) in a randomised, placebo-controlled trial. A significant reduction of anginal attacks (p = 0.03) was demonstrated only during the first day of treatment. The lack of significant effects during the following two days was ascribed partly to the possible development of nitrate-tolerance, partly to a declining number of anginal attacks in the placebo-group during the trial period, for which reason the difference between the actively treated and the placebo group became smaller and finally the consumption of nicomorphine was considerably greater in the placebo group.

One hundred ninety patients with chronic angina for an average of 2 years were followed. Forty-seven had at least 1 mm of ST deviation in response to provocation of coronary vasoconstriction by prolonged hyperventilation (group I); 143 had no ST deviation (group II). The angiographic response to this test was studied in 21 patients from group I, and revealed 25 to 100% diameter reduction; in group II 9 patients showed a 5 to 14% diameter reduction. In group I, 15 patients (32%) died (hazard rate = 0.17 deaths/patients X years) vs 18 (13%) in group II (hazard rate = 0.06) (p less than 0.01). Seven patients in group I (15%) and 3 in group 2 (2%) died while waiting for surgery (p less than 0.01). All patients who died had coronary stenoses of at least 70%. A Cox regression analysis, using 24 variables (invasive and noninvasive), showed a positive hyperventilation test (ST deviation at least 1 mm), low ejection fraction and systolic blood pressure of at least 160 mm Hg to be independent predictors of death (p less than 0.05). Considering only deaths in non-operated patients (patients waiting for surgery and patients not planned to undergo operation), a rate-pressure product/100 of 150 or less at exercise stress testing, left ventricular end-diastolic pressure of 15 mm Hg or more and duration of angina less than 1 year were also independent predictors of death. Thus, the hyperventilation test may be useful for identifying angina patients who are at high risk of cardiac death due to dynamic coronary obstructions.

We studied the exercise stress test and the coronary artery tone in two groups of angina patients with comparable coronary atherosclerosis. Group I (20 males and 5 females, mean age 53.5 years) with a positive, and group II (22 males and 3 females, mean age 52.5 years) with a negative response to the hyperventilation test (HVT). A positive exercise stress test (ST depression greater than or equal to 1 mm) was found in 24 patients in group I vs. 15 in group II (p less than 0.01), despite a lower maximal rate pressure product (198 +/- 11.2 vs. 236 +/- 10.1, p less than 0.05) and maximal work load (110 W +/- 7.1 vs. 136 +/- 7.4 W, p less than 0.02) in group I. A high coronary artery tone (dilatation (DIL%) of the coronary arteries after nitroglycerin greater than or equal to 10%) was found in 18 patients in group I and in 4 in group II (p less than 0.01). DIL% was 22.6 +/- 3.8 vs. 5.8 +/- 1.4 in groups I and II, respectively (p less than 0.005). DIL% was significantly related to persistence of ST depression after exercise (r = 0.36, p less than 0.05), and 21 of 22 patients with high tone had a positive exercise stress test vs. 18 of 28 with low tone (p less than 0.05). These findings suggest that the coronary artery tone influences the response to exercise in some patients with angina. Since the patients in group I were identified by HVT, our results underline the clinical relevance of this test.