Lifestyle changes and heart disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R L Kirkeeide.
Explore the source record for details and available documents.
In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.
Coronary vasomotion of normal, stenotic, and poststenotic vessel segments was studied in 18 patients with coronary artery disease at rest, during submaximal bicycle exercise, and 5 min after sublingual nitroglycerin or oral isosorbide-dinitrate (ISDN) spray. Patients were divided into two groups: group 1 consisted of 10 patients with no premedication prior to exercise, and group 2 consisted of 8 patients receiving 120 mg long-acting ISDN orally 1 h before the procedure. Quantitative coronary arteriography was carried out in biplane projection using a semi-automatic computer system. The normal vessel segment showed a trend toward a small increase in cross-sectional area during exercise in both groups (+3% in group 1 and +4% in group 2, both NS). After sublingual nitroglycerin following exercise, there was a significant increase in group 1 (+29%, p less than 0.001 vs rest) but not after ISDN spray in group 2 (+5%, NS vs rest). The stenotic vessel segment showed exercise-induced stenosis narrowing in group 1 (-31%, p less than 0.01 vs rest) which was prevented by oral ISDN (+6%, NS vs rest). After exercise, sublingual administration of nitroglycerin or ISDN spray was associated with no significant change in stenosis area in either group. The poststenotic vessel segment showed no significant vasomotion during exercise in both groups (area change +6% in group 1 and +7% in group 2), but poststenotic luminal area increased after sublingual nitroglycerin (group 1: +15%, p less than 0.01 vs rest) or ISDN spray (group 2: +15%, p less than 0.05 vs rest). The mean pulmonary artery pressure increased during exercise from 22 to 39 mmHg (p less than 0.001) in group 1 and from 14 to 27 mmHg (p less than 0.001) in group 2. At rest (p less than 0.001) and during exercise (p less than 0.01) mean pulmonary pressure was lower in group 2 than in group 1. Thus, it is concluded that coronary vasomotion of the poststenotic vessel segment is only minimal during exercise and is not affected by coronary vasomotion of the stenotic vessel segment. Pretreatment with oral ISDN did not influence coronary vasomotion of the poststenotic vessel segment, but prevented exercise-induced stenosis narrowing. In the untreated patients, vasoconstriction of the stenotic vessel segment is limited to the site of the stenosis, and it appears that there is no release of vasoactive substances with vasoconstrictive influences on the poststenotic segment.
In a collaboration between the University of Texas (software) and the University of Zürich (hardware) a compact, automatic system for biplane quantitative coronary arteriography was developed. The system is based on a 35 mm film projector, a slow-scan CCD-camera (image digitizing) and a computer workstation (Apollo DN 3000, image storage and processing). A new calibration procedure based on two fixed reference points in the center of the image intensifier was used (isocenter technique). Contour detection of coronary arteries was carried out in biplane projection using a geometric-densitometric edge-detection algorithm. The proximal and distal luminal areas, as well as the minimal luminal area of the stenotic vessel segment were determined. Accuracy and precision were determined from precision drilled holes in a plexiglas cube which were filled with 50%, 75% and 100% contrast medium. The diameter of the holes ranged from 0.5 to 5.0 mm. The mean difference and the standard deviation of the differences between the true and the measured diameters were 0.12 +/- 0.14 mm for plane A and 0.26 +/- 0.17 mm for plane B, respectively. After a second order correction the mean difference amounted to 0.02 +/- 0.09 mm for plane A and 0.02 +/- 0.12 mm for plane B, respectively. Intra- and interobserver variability were evaluated in 5 patients (age 60 +/- 10 years) with coronary artery disease using 16 normal and 5 stenotic vessel segments (cross-sectional area ranging from 0.8 to 8.7 mm2). Two independent observers analyzed the same vessel segment twice. Intraobserver variability expressed as the standard error of estimate in percent of the mean angiographic vessel area (SEE) amounted to 2.1% for observer 1 and 4.4% for observer 2, respectively. Interobserver variability expressed as SEE was 4.1% for measurement 1 and 3.6% for measurement 2, respectively.
PART I: Coronary flow reserve indicates functional stenosis severity, but may be altered by physiologic conditions unrelated to stenosis geometry. To assess the effects of changing physiologic conditions on coronary flow reserve, aortic pressure and heart rate-blood pressure (rate-pressure) product were altered by phenylephrine and nitroprusside in 11 dogs. There was a total of 366 measurements, 26 without and 340 with acute stenoses of the left circumflex artery by a calibrated stenoser, providing percent area stenosis with flow reserve measured by flow meter after the administration of intracoronary adenosine. Absolute coronary flow reserve (maximal flow/rest flow) with no stenosis was 5.9 +/- 1.5 (1 SD) at control study, 7.0 +/- 2.2 after phenylephrine and 4.6 +/- 2.0 after nitroprusside, ranging from 2.0 to 12.1 depending on aortic pressure and rate-pressure product. However, relative coronary flow reserve (maximal flow with stenosis/normal maximal flow without stenosis) was independent of aortic pressure and rate-pressure product. Over the range of aortic pressures and rate-pressure products, the size of 1 SD expressed as a percent of mean absolute coronary flow reserve was +/- 43% without stenosis, and for each category of stenosis severity from 0 to 100% narrowing, it averaged +/- 45% compared with +/- 17% for relative coronary flow reserve. For example, for a 65% stenosis, absolute flow reserve was 5.2 +/- 1.7 (+/- 33% variation), whereas relative flow reserve was 0.9 +/- 0.09 (+/- 10% variation), where 1.0 is normal. Therefore, absolute coronary flow reserve by flow meter was highly variable for fixed stenoses depending on aortic pressure and rate-pressure product, whereas relative flow reserve more accurately and specifically described stenosis severity independent of physiologic conditions. Together, absolute and relative coronary flow reserve provide a more complete description of physiologic stenosis severity than either does alone. PART II: Coronary flow reserve directly measured by a flow meter is altered not only by stenosis, but also by physiologic variables. Stenosis flow reserve is derived from length, percent stenosis, absolute diameters and shape by quantitative coronary arteriography using standardized physiologic conditions. To study the relative merits of absolute coronary flow reserve measured by flow meter and stenosis flow reserve determined by quantitative coronary arteriography for assessing stenosis severity, aortic pressure and rate-pressure product were altered by phenylephrine and nitroprusside in 11 dogs, with 366 stenoses of the left circumflex artery by a calibrated stenoser providing percent area stenosis as described in Part I.(ABSTRACT TRUNCATED AT 400 WORDS)
At present, coronary collateralization cannot be identified or assessed noninvasively in patients. In animal studies, coronary collaterals are associated with coronary steal, defined as a regional fall in perfusion during coronary arteriolar vasodilation. To determine the effect of coronary arteriolar vasodilation on collateral bed perfusion in man, myocardial perfusion imaging was performed before and after pharmacologic coronary vasodilation in patients with coronary artery disease (CAD). Regional myocardial activity of 82Rb or 13N ammonia was measured by positron emission tomography (PET) at rest and with intravenous dipyridamole/handgrip stress in 28 patients with angiographic collaterals and in 25 control patients with similar CAD severity by quantitative arteriography. Regional myocardial activity decreased after dipyridamole, indicating coronary steal, in 25 of 28 patients with angiographic collaterals and in only 4 of 25 control patients without angiographic collaterals. These findings suggest that developed collaterals are associated with myocardial steal in patients with CAD, allowing potential use of PET for non-invasive identification of coronary collateralization.
To assess the accuracy of positron emission tomography (PET) for evaluation of coronary artery disease (CAD), cardiac PET perfusion images were obtained at rest and with dipyridamole-handgrip stress in 193 patients undergoing coronary arteriography. PET images were reviewed by two independent readers blinded to clinical data. Subjective defect severity scores were assigned to each myocardial region on a 0 (normal) to 5 (severe) scale. Results were compared with arteriographic stenosis severity expressed as stenosis flow reserve (SFR), with continuous values ranging from 0 (total occlusion) to 5 (normal), calculated from quantitative arteriographic dimensions using automated detection of the vessel borders. There were 115 patients with significant CAD (SFR less than 3), 37 patients with mild CAD (3 less than or equal to SFR less than 4), and 41 patients with essentially normal coronaries (SFR greater than or equal to 4). With increasingly severe impairment of stenosis flow reserve, subjective PET defect severity increased. Despite wide scatter, a PET score of 2 or more was highly predictive of significant flow reserve impairment (SFR less than 3). For each patient, the score of the most severe PET defect correlated with the SFR of that patient's most severe stenosis (rs = 0.77 +/- 0.06). For each of 243 stenoses, PET defect score correlated with the SFR of the corresponding artery (rs = 0.63 +/- 0.08). PET defect location closely matched the region supplied by the diseased artery, and readers agreed whether the most severe PET defect was less than or more than 2 for 89% of patients.
To determine the relation between stenosis anatomy and perfusion in man, 31 patients had quantitative coronary arteriography and positron imaging (PET) with Rb-82 or N-13 ammonia at rest and after dipyridamole-handgrip stress. 10 patients were also studied after angioplasty (total stenoses = 41). Percent narrowing and absolute cross-sectional luminal area were related through a quadratic function to myocardial perfusion reserve determined with PET. Arteriographically determined coronary flow reserve was linearly related to relative myocardial perfusion reserve as expected, based on the derivation of equations for stenosis flow reserve. All of the correlations had considerable scatter, indicating that no single measurement derived by coronary arteriography was a good indicator of perfusion reserve by PET in individual patients. This study provides the relation between all anatomic dimensions of coronary artery stenoses and myocardial perfusion reserve in man, and suggests that PET indicates the functional significance of coronary artery stenoses for clinical purposes.
The effect of percutaneous transluminal coronary angioplasty (PTCA) on myocardial perfusion reserve has not been previously determined. Accordingly, 11 patients underwent positron imaging with [13N]ammonia or 82Rb at rest and following dipyridamole + handgrip stress before and after PTCA. The ratio of stress to rest activity (S:R) was determined for each region of interest. Relative myocardial perfusion reserve by positron tomography (RMPR) was calculated by dividing S:R of the stenotic area by a corresponding value from a normal reference area of the same patient. Automated quantitative coronary arteriography was used to objectively measure the percent diameter (%D) and the percent area narrowing (%A) of the stenoses. In nine patients with successful PTCA, %D and %A improved (68 +/- 10 to 49 +/- 15% and 92 +/- 3 to 72 +/- 5%) and RMPR increased from 0.79 +/- 0.07 to 0.96 +/- 0.05. In the two patients in whom PTCA was unsuccessful, RMPR was unchanged. Changes in RMPR correlated inversely with changes in %D (r = -0.68) and %A (r = -0.92) and directly with improved coronary flow reserve derived from all stenosis measurements (r = 0.73, p less than 0.001 for each). This study suggests that dipyridamole + handgrip stress imaging with PET can be used to assess changes in myocardial perfusion reserve before and after PTCA with the potential for determining restenosis noninvasively.
The purpose of this study was to determine whether coronary flow reserve measured by flow meter correlated with or could be predicted by quantitative coronary arteriography accounting for all dimensions of a coronary artery stenosis. Five dogs were chronically instrumented with an inflatable stenosing cuff, a Doppler flow velocity meter, proximal and distal coronary artery catheters and aortic and pulmonary artery catheters. For 18 stenoses over a wide range of severity, orthogonal coronary arteriograms were analyzed quantitatively at rest to predict coronary flow reserve based on fluid dynamic equations. The X-ray-predicted coronary flow reserve correlated closely with that measured directly by implanted flowmeter with an r value of 0.91, a regression equation of X-ray-predicted coronary flow reserve = 1.08 (measured coronary flow reserve) - 0.08 and 95% confidence limits (+/- 2 SD) of 0.66. Neither percent diameter narrowing alone nor absolute stenosis diameter alone correlated well with measured coronary flow reserve. Results confirm that coronary flow reserve is a single integrated measure of coronary stenosis severity reflecting all its geometric dimensions. Flow reserve correlated closely with and was accurately predicted by quantitative coronary arteriography taking into account all stenosis dimensions. This study establishes the theoretical and experimental basis for using coronary flow reserve as a single, integrated functional measure of stenosis severity reflecting all of its geometric characteristics.
The purpose of this study was to determine the clinical feasibility of diagnosing significant coronary artery disease by positron imaging of myocardial perfusion without a cyclotron, using generator-produced rubidium-82 (82Rb). Fifty patients underwent positron emission tomography of the entire heart using a multislice positron camera and intravenous 82Rb or nitrogen-13 ammonia (13NH3) before and after intravenous dipyridamole combined with handgrip stress. Images were read by two observers blinded as to clinical or arteriographic data. Automated quantitative coronary arteriography was obtained for the arteriographic determination of coronary flow reserve, previously demonstrated to be a single integrated measure of stenosis severity accounting for all its geometric dimensions of length, absolute diameter, percent narrowing and asymmetry by quantitative analysis of cine films. Significant coronary artery disease was defined as an arteriographically determined coronary flow reserve of less than 3.0 based on all stenosis dimensions. Any single geometric measure of stenosis severity alone was an inadequate reference standard for comparison with perfusion images. Sensitivity of identifying patients with coronary artery disease having an arteriographically determined coronary flow reserve of less than 3.0 was 95% by positron imaging with a specificity of 100%. The single case that was missed, studied with 13NH3, had a 43% diameter narrowing of a small ramus intermedius off the left coronary artery with no significant narrowing of the major coronary arteries. Positron emission tomography of myocardial perfusion before and after intravenous dipyridamole combined with handgrip stress utilizing generator-produced 82Rb provides sensitive and specific diagnosis of reduced coronary flow reserve due to coronary artery disease in humans.
This report describes a patient with persistent, recurrent left anterior descending coronary artery spasm, which causes marked left ventricular dysfunction in a clinical course that is typical of acute myocardial infarction with hyperacute electrocardiographic changes. However, after emergency coronary artery bypass surgery, the patient had complete reversal of left ventricular dysfunction, with no residual evidence of acute myocardial infarction by electrocardiograph or gated blood pool imaging and no CPK enzyme rise. The patient therefore demonstrates that coronary spasm in some instances clearly precedes the sequence of pathophysiologic events leading to acute myocardial infarction. Our report also demonstrates for the first time in man that massive left ventricular dysfunction may occur in this intermediate coronary syndrome, presenting clinically as impending myocardial infarction. With aggressive surgical intervention and emergency bypass surgery, left ventricular function was restored to normal. Despite the semantic problems of categorizing such patients as having impending myocardial infarction, the severe left ventricular dysfunction and alarming course of this patient's illness was resolved by emergency surgery, suggesting that, in some instances, aggressive therapy is warranted.
It has been suggested that vasodilation distal to a stenosis may cause a profound decrease in perfusion pressure and adversely affect regional left ventricular function. This phenomenon could explain the clinical concept of reversal of regional dysfunction by coronary revascularization. To evaluate the hypothesis that regional myocardial function parallels regional coronary blood pressure in the absence of changes in coronary flow, dogs chronically instrumented with left circumflex coronary artery flow probes, cuff occluders, pressure catheters and segmental function sonomicrometers were studied. By decreasing regional coronary vascular resistance with selective intracoronary dipyridamole and controlling blood flow with a proximal coronary cuff occluder, the mean left circumflex artery pressure was reduced from 83 +/- 3 to 38 +/- 2 mm Hg while circumflex coronary blood flow was maintained constant. Regional contractile function as measured by circumflex sonomicrometers was unchanged at constant circumflex subendocardial blood flow as measured by radioactive microspheres. These findings suggest that regional contractile function is dependent on subendocardial blood flow and is independent of coronary perfusion pressure.
Explore the source record for details and available documents.
Depressed left ventricular function during the early part (first third) of both systole and diastole in the resting state have been reported to be sensitive indicators of coronary artery disease in patients with normal global function at rest. To evaluate the possible mechanisms of these findings, 11 dogs were chronically instrumented with segmental function sonomicrometers in the left circumflex and left anterior descending coronary artery distribution, circumflex coronary flow probes and cuff occluders, aortic flow probes and ventricular pressure transducers. Percent segmental function during the first third of systole and diastole was measured in the control state and with graded circumflex artery flow reductions. Significant decreases in early systolic function with ischemia in the circumflex artery distribution were partially offset by compensatory augmented shortening in the left anterior descending artery distribution. With ischemia in the circumflex distribution, there was prolonged contraction into diastole manifested as impaired relaxation. Simultaneously, in the left anterior descending artery distribution, there was minimal compensatory enhanced relaxation. These results suggest that early systolic dysfunction in ischemic segments may be offset by enhanced function in nonischemic segments, rendering minimal, if any, change in global systolic function. Early diastolic dysfunction in ischemic segments exceeds compensatory changes in nonischemic areas by two-to-four-fold. Hence, early diastolic functional indexes may be more sensitive indicators of ischemia at rest than early systolic functional indexes.
Explore the source record for details and available documents.
This study is concerned with the pressure drop that develops across an arterial stenosis, with particular emphasis on the effect of the stenosis at high blood flow rates induced by a locally administered vasodilator drug. Stenoses, ranging in severity from 55.7% to 91.0% reduction in lumen area were artificially induced in the femoral and carotid arteries of large mongrel dogs. Instantaneous flow rates and pressure drops were measured over a wide range of flow conditions. Mean velocities varied from 3.9 to 88.8 cm/sec. Experimental data support the applicability of a relatively simple equation for predicting the pressure drop over this wide range of velocities and stenosis geometries. Results show that blood flow through a particular artery can increase by a large factor, in the range of 4-5, under conditions of vasodilation with a corresponding large decrease in pressure distal to the stenosis. The pressure drop increases in a nonlinear manner with velocity and thereby accentuates the importance of the stenosis at elevated flow rates. We suggest that a critical stenosis be defined in terms of its effect on maximal flow rather than resting flow.