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Coronary vasodilators have been variously reported to increase, decrease, or have no effect upon blood flow to ischemic myocardium. Consequently, the effects of two different types of dilators, nitroglycerin (TNG) and dipyridamole, were studied with radioactive microspheres in open-chested dogs after coronary artery ligation. Given as a bolus i.v. injection 0.4 mg TNG resulted in an increase in blood flow to nonischemic areas of myocardium and a preservation of flow to ischemic regions, despite a fall in blood pressure. 5 min later blood pressure and nonischemic flow were back to base line, and a small selective increase in flow to ischemic myocardium was found (0.15-0.18 ml/min per g, P less than 0.05). During an 0.2 mg/min infusion of TNG, and also after 1 mg/kg i.v. dipyridamole, ischemic flow was maintained in the face of a 20-30% reduction in blood pressure. In this setting, nonischemic flow was unchanged during TNG and doubled after dipyridamole. With the addition of methoxamine in both dilator groups, blood pressure returned to base line while flow to ischemic areas increased above base-line values (TNG, 0.16-0.20 ml/min per g, P less than 0.01; dipyridamole, 0.18-0.31 ml/min per g, P less than 0.05). Epicardial ST segment elevations increased during TNG infusion and were unchanged after dipyridamole, but with addition of methoxamine, ST segments became less elevated in both drug groups, concomitant with the observed increase in collateral blood flow. These data indicate that both types of coronary vasodilators, when used in conjunction with methoxamine to support blood pressure, reduce collateral resistance, increase collateral flow, and reduce epicardial ST-segment elevations.

This study was conducted to determine whether low level exposure to carbon monoxide would increase myocardial ischemia associated with acute myocardial infarction. An hour after coronary artery ligation, eleven anesthetized dogs underwent five sequential respiratory exposures to 5,000 ppm carbon monoxide, producing mean blood carboxyhemoglobin levels of 4.9% to 17.0%. Ischemia, as indicated by the amount of S-T segment elevation in epicardial electrocardiograms, increased significantly at the lowest carboxyhemoglobin level and increased further with increasing carbon monoxide exposure. These changes occurred in the absence of altered heart rate, blood pressure, left atrial pressure, cardiac output, or blood flow to ischemic myocardium. Flow to non-ischemic myocardium increased with carbon monoxide exposure, the percentage increase being approximately double the increase in carboxyhemoglobin level. Thus, low level exposure to carbon monoxide can significantly augment ischemia in acute myocardial infarction, apparently through a reduction in oxygen supplied to ischemic tissue. The data suggest that hypoxia induced by carbon monoxide exposure is more severe than can be accounted for by a simple reduction in oxygenated hemoglobin.

The cumulative effects of repeated, brief episodes of regional ischemia on myocardial function and dimension were examined in 14 open-chest dogs. The left anterior descending coronary artery was occluded for 5 minutes, followed by 10 minutes of reflow, repeated 16 times, and then 1 hour recovery. Systolic function decreased progressively in segments made repetitively ischemic and remained depressed even after 1 hour of recovery. Average systolic shortening decreased 20% from baseline after recovery from the first occlusion, 82% after the 8th, 91% after the 16th, and 104% after the 1 hour recovery (p less than 0.015, analysis of variance). End-diastolic segment length progressively increased in regions made repetitively ischemic, lengthening 4% after the first occlusion, 10% after the third occlusion, 19% after the sixteenth occlusion, and 16% after 1 hour of recovery (p less than 0.02). Nonischemic end-diastolic segment length also showed a smaller but parallel increase, while non-ischemic systolic function showed compensatory improvement. After the dogs were killed, myocardial staining with triphenyl tetrazolium chloride revealed no necrosis. Electron microscopy, performed in 5 dogs, showed scattered mitochondrial swelling in both postischemic and nonischemic regions, but no evidence of irreversible injury. The ratio of myocardial blood flow in the region made repetitively ischemic to nonischemic flow, as measured with microspheres, was 1.00 +/- 0.02 before the occlusions and 0.90 +/- 0.03 just before death (difference not significant). Thus, in the dog progressively abnormal regional systolic function and regional and global diastolic dilatation can be produced by repetitive, brief, coronary occlusions, which are not associated with histochemical or ultrastructural evidence of myocardial necrosis.

A study was undertaken to determine whether barbiturate anaesthesia, with or without thoracotomy, adversely affects collateral blood flow during acute coronary artery occlusion. Twelve dogs were instrumented with an electromagnetic flow probe and pneumatic occluder on the left circumflex artery; seven days later, in the conscious state, complete coronary artery occlusion was induced for 8 min. Heart rate, mean aortic pressure, and subendocardial and subepicardial blood flow in the ischaemic zone were measured by radioactive microspheres before and 5 min into coronary artery occlusion. Measurements were repeated after pentobarbital 30 mg.kg-1 (n = 7) and after pentobarbital plus thoracotomy (n = 12). Compared with the conscious state, pentobarbital and thoracotomy produced a decrease in endocardial blood flow in the ischaemic zone (0.21(0.04) to 0.15(0.03) ml.min-1.g-1) and a modest redistribution from endocardium to epicardium (ratio of endocardial to epicardial flow 0.55(0.06) to 0.49(0.07) ml.min-1.g-1), coincident with an increase in heart rate from 127 to 178 beats.min-1 but no change in mean arterial pressure. Directionally similar, but smaller, changes occurred during anaesthesia without thoracotomy. To determine the role of tachycardia five of the animals were studied in the conscious state during a 50% increase in heart rate induced by atrial pacing. A similar decrease occurred in coronary blood flows as with anaesthesia. The results indicate that barbiturate anaesthesia and thoracotomy produce a diminution in collateral flow to ischaemic myocardium, together with an accentuation of its transmural maldistribution, and suggest that anaesthetic induced tachycardia is primarily responsible for these flow alterations.

The influence of afterload resistance on the end-systolic pressure-thickness relationship (ESPTR) was assessed in six isolated canine left ventricles made to eject into a simulated arterial system. An increase of simulated peripheral resistance from 1.5 to 6.0 mmHg.s.ml-1 resulted in a modest but significant shift of the ESPTR upward and to the right, indicating augmented contractile performance. A relationship between the extent of systolic wall thickening and end-systolic performance was also observed: increased wall thickening impairing and decreased wall thickening enhancing end-systolic performance. The dependence of end-systolic performance on wall thickening history in this setting is consistent with shortening deactivation. This phenomenon appears to account at least in part for the observed shift in the ESPTR with altered afterload resistance.

The respective importance of flow and cellular viability in determining initial myocardial thallium uptake was studied in reperfused and nonreperfused experimental myocardial infarction. Open-chest dogs were subjected to permanent coronary artery occlusion of 70-minute (n = 3) or 5-hour duration (n = 5), or to a 3-hour temporary occlusion followed by reflow (n = 14). Thallium uptake 10 minutes after intravenous injection was compared directly with radioactive microspheres in myocardial samples from excised hearts. Triphenyl tetrazolium chloride staining was used to differentiate necrotic and viable samples with confirmation by electron microscopy. In nonreperfused infarcts, thallium uptake occurred despite necrosis, and a close correlation was found between thallium uptake and regional myocardial blood flow. In reperfused infarcts, thallium uptake again occurred, but was reduced relative to flow in necrotic myocardium and, to a lesser extent, in reperfused viable areas. However, because of the high levels of reflow, actual thallium uptake was often more than 50% of normal in reperfused necrotic regions. This study demonstrates that the presence of thallium uptake is an unreliable indicator of myocardial injury and that reperfused necrotic tissue may have remarkably high levels of thallium uptake.

Although thallium-201 is known to redistribute slowly into regions of ischemic myocardium after restoration of blood flow, it is not clear to what extent normalization of flow is an essential requirement for the redistribution process. In a search for a flow-independent component of thallium redistribution, 12 dogs with stenosis of the circumflex coronary artery underwent atrial pacing for either 20 minutes (group I, 6 dogs) or 2 hours (group II, 6 dogs). Radioactive thallium and radioactive microspheres, 7 to 10 mu, were injected after 10 minutes of atrial pacing in both groups. Pacing resulted in a 40 percent reduction in subendocardial blood flow to the circumflex-perfused myocardium in both groups I and II. This relative reduction in flow was maintained at a stable level over the 2 hour pacing period in group II. Thallium activity in the relatively ischemic zone was significantly greater in dogs with 2 hours of pacing (group II) than in those with 10 minutes of pacing (group I). Redistribution of thallium occurred despite the continued presence of reduced flow in circumflex-perfused endocardial tissue. These data suggest that a significant component of thallium redistribution may be flow-independent.

It has been shown previously that 30-minute infusions of intravenous nitroglycerin in patients with acute myocardial infarction are able to lower left ventricular filling pressure and improve left ventricular function while lowering mean arterial pressure by only 7 mmHg (0.9 kPa). A decrease in sigmaST in praecordial ST segment mapping studies during nitroglycerin infusion in patients with anterior infarction suggested a decrease in the extent of myocardial ischaemia. In the present study, 30 patients with acute myocardial infarction received 1- to 3-hour infusions of intravenous nitroglycerin at infusion rates sufficient to lower mean arterial pressure by an average of 22 mmHg (2.9 kPa). An improvement in ventricular function was noted in that subgroup of patients with the msot severe left ventricular dysfunction. All patients with anterior myocardial infarction underwent serial ST segment mapping and, irrespective of the presence or absence of left ventricular failure, showed a decrease in sigmaST during nitroglycerin infusion (P less than 0.005). These findings suggest that infusion of nitroglycerin improves left ventricular function and/or alters left ventricular compliance in patients with left ventricular failure complicating myocardial infarction and furthermore decreases sigmaST in all patients, irrespective of the presence or absence of left ventricular failure, suggesting that the extent of myocardial ischaemia is decreased.

Two hundred consecutive catheterized patients with unstable angina pectoris were reviewed to find clinical and noninvasive indicators of left main coronary artery disease (greater than or equal to 50% lesion). Thirty-five patients (17.5% of total) had left main coronary artery disease. There were no differences between patients with and without left main coronary artery disease in age, sex, results of resting electrocardiogram, congestive heart failure, dyspnea during pain, duration of longest pain, arrhythmias, response to medical therapy, or other risk factors. Crescendo angina pectoris (worsening of pre-existing angina), transient ST-segment depression with pain, simultaneous anterior and inferior ST changes during pain, and fluoroscopic calcification of the left main coronary artery were all significantly more common in patients with left main coronary artery disease. However, low sensitivity or low predictive value, or both, limit the usefulness of these clinical predictors. Left main coronary artery disease cannot be reliably predicted in patients with unstable angina pectoris before coronary arteriography.

To evaluate the effect of dipyridamole on regional wall motion after myocardial infarction two-dimensional echocardiograms were obtained on 21 postinfarction patients immediately before and 7 to 10 minutes after the intravenous infusion of ddipyridamole (0.60 mg/kg). All patients underwent coronary angiography, and 20 patients underwent scintigraphy with dipyridamole thallium immediately subsequent to dipyridamole echocardiography. Dipyridamole augmented noninfarct zone regional wall motion in 20 of 31 regions supplied by nonstenotic coronary arteries. In contrast, only one of eight regions of noninfarct zone myocardium supplied by coronary arteries with greater than a 70% luminal diameter narrowing (vulnerable myocardium) was able to augment the regional wall motion subsequent to dipyridamole administration (p = 0.05). Dipyridamole echocardiography appears to be a safe and sensitive technique that may be useful in the detection of vulnerable myocardium in the early postinfarction period.

Prior studies of the contribution of coronary disease risk factors to familial aggregation of premature coronary disease may have underestimated risk factors by relying on self-reported risk factor prevalence levels or, when risk factors have been measured, by using cut points in excess of the 90th percentile. To determine the actual prevalence of hyperlipidemia, hypertension and diabetes, and the awareness of these coronary risk factors in unaffected family members, 150 apparently coronary disease-free siblings of 86 people who had documented coronary disease before 60 years of age were studied. All subjects participated in a 1 day screening preceded by a self-administered risk factor questionnaire and a personal interview. Participation of both the index patients and siblings exceeded 86%. With the use of nationally established recommendations for blood pressure and lipids, which are based on coronary disease risk curves, screening revealed that 48% of brothers and 41% of sisters were hypertensive, 45% of brothers and 22% of sisters had a lipid abnormality, 38% of siblings were current cigarette smokers and 4.7% were diabetic. Two or more risk factors were present in 42% of brothers and 26% of sisters. More than 75% of siblings had one or more risk factors that would require intervention. When compared with a race-, gender- and age-matched reference population from the Lipid Research Clinics Prevalence Study, distributions for blood pressure and for total and low density lipoprotein cholesterol were higher for the siblings in every gender and age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Radioactive microspheres were used to determine the pattern of regional left ventricular blood flow 30-60 min after acute coronary artery occlusion in nine dogs. Flow was found to be markedly reduced in the centre but only moderately reduced toward the edge of the ischaemic lesion, while in surrounding non-ischaemic myocardium flow was greater than normal. Flow was evenly distributed through the ventricular wall in non-ischaemic areas, but in ischaemic ones there was a disproportionate reduction in flow to the inner half of the wall.

An early systolic notch on the upstroke of the apexcardiogram (ACG) has previously been reported to occur in mobile left atrial myxoma but has not been noted in valvular mitral stenosis. It has therefore been considered a useful diagnostic sign for myxoma. We report four patients with mitral valve stenosis who had an early systolic notch in the ACG. Myxoma was excluded by catheterization and/or surgery. We feel that the notch is not specific for myxoma and that its finding should be interpreted with caution.

Simultaneous recordings were made of the apexcardiogram (ACG), phonocardiogram, left atrial and left ventricular (LV) pressures, and electrocardiogram at the time of cardiac catheterization in a patient with a mobile myxoma of the left atrium. Notches on the upstroke of the ACG and LV pressure were demonstrated and were shown to coincide exactly. It is suggested that the notch on the ACG, like that on the LV pressure, is related to sudden movement of the tumor from left ventricle to left atrium, and is therefore a useful diagnostic sign of mobile left atrial myxoma.

Background Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants. Methods We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis. Results Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p

Among patients with unstable angina pectoris, those with crescendo angina seem to be at high risk for death and myocardial infarction. We reviewed the clinical, arteriographic, and hemodynamic findings in 218 consecutive catheterized patients with unstable angina. Unstable angina was defined as ischemic cardiac pain at rest associated with transient ECG changes but no evidence for acute myocardial infarction. Patients were divided into two groups according to the duration of symptoms: 134 patients with crescendo angina (new, or increasing, rest pain with previous ischemic symptoms present for more than three months) and 84 with recent onset angina (symptoms present for less than three months). Compared with patients with recent onset symptoms, patients with crescendo angina had more extensive coronary disease and lower ejection fractions, which may explain their poor prognosis. ( JAMA 244:574-576, 1980)

The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis.

Sodium nitroprusside was administered intravenously to a patient critically ill with severe mitral insufficiency caused by leakage around a prosthetic mitral valve. Cardiac index increased (1.3 to 3.2 liters/min/sq m) and regurgitant fraction and volume decreased (0.93 to 0.74 for regurgitant fraction, and 16.1 liters/min/sq m to 9.8 liters/min/sq m for regurgitant volume), in association with dramatic clinical improvement. It is suggested that nitroprusside therapy, by decreasing impedance to forward left ventricular output, may be of particular benefit to patients with severe mitral regurgitation. ( JAMA 230:1011-1013, 1974)

• There are two broad classes of angina pectoris, related to two fundamentally different pathogenetic mechanisms: in classic angina, atherosclerotic narrowings limit the ability of the coronary arteries to augment myocardial blood flow in response to increases in demand, and in variant angina, a primary reduction in coronary blood flow occurs, unrelated to changes in demand. Over the last decade, major advances have been made in our understanding of the factors that control coronary blood flow and how they interact in each of the major classes of angina. The present review examines these advances, as well as their relation to the syndromes of rest angina, postprandial angina, and exertional coronary artery spasm. Current knowledge about the mechanism by which myocardial ischemia produces the sensation of angina is discussed, along with the application of pathogenetic principles to medical therapy. (Arch Intern Med1982;142:1685-1692)

To document optimal sampling frequency, we reviewed creatine kinase (CK) myocardial specific isoenzyme (CKMB) results in 314 patients with suspected acute myocardial infarction (MI). In 127 patients with elevated CK/CKMB, peak CK observed using all samples (every four-hour [Q4hr] method) was compared with results that would have been obtained had samples been taken on admission and either twice daily (every 12-hour [Q12hr] method) or once daily (every 24-hour [024hr] method). Although average peak CK was statistically different (Q4hr>Q12hr>Q24hr), major underestimation of peak CK (≥500 units/L) was uncommon (3%) using the Q12hr method, suggesting that Q12hr sampling is a practical, cost-effective approach for patients with suspected acute MI. ( JAMA 1983;249:393-394)

Thirty-five patients with atypical chest pain were given ergonovine maleate as a provocative test for coronary spasm. None of the patients had significant coronary atherosclerosis. The patients were divided into two groups based on clinical information available before ergonovine testing. Group 1 patients (n=13) had objective evidence of cardiac disease manifested by episodes of syncope, ventricular tachyarrhythmias, myocardial infarction, or transient ST segment shifts with chest pain. Group 2 patients had chest pain but no objective evidence of cardiac disease. The ergonovine test was positive in 11 of 13 patients in group 1. None of the 22 group 2 patients had a positive response to ergonovine. These data suggest that ergonovine testing does not allow for any more precise recognition of patients with atypical chest pain who have coronary artery spasm than do clinical data alone. ( JAMA 242:2858-2861, 1979)