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Biomedical subjects

F H Sheehan

Publications and source records attributed to F H Sheehan.

At least 73 records · Page 4Linked to original sources
PubMed1987

Determinants of improved left ventricular function after thrombolytic therapy in acute myocardial infarction.

Many studies have been performed to evaluate the efficacy of thrombolytic therapy in achieving reperfusion, salvaging myocardium and enhancing survival. This review discusses the concordance between the results of these clinical studies and the observations made in experimental animals of the effect of reperfusion on the recovery of left ventricular function. The evaluation of functional recovery is affected by the timing of the measurement and the sensitivity of the method for detecting regional abnormalities. In addition, the underlying coronary anatomy also determines outcome, so that infarct location, collateral circulation and the degree of coronary obstruction merit consideration. Two factors are of paramount importance in determining the amount of myocardium salvaged, the recovery of left ventricular function and the reduction in mortality. These factors are: the time delay until reperfusion is achieved and the adequacy of the coronary reflow. The close agreement between studies measuring the effect of reperfusion on left ventricular function and studies with mortality as the end point provides indirect evidence that enhancement of survival in patients treated with thrombolytic agents is mediated by recovery of ventricular function.

Angioplasty, Balloon↗
PubMed1987

The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI Phase I) trial.

In Phase I of the NHLBI trial of Thrombolysis in Myocardial Infarction (TIMI), 290 patients admitted within 7 hr after onset of acute infarction were randomly assigned to intravenous treatment with either streptokinase (SK) or recombinant tissue-type plasminogen activator (rt-PA). Left ventricular function was measured from contrast ventriculograms in 145 patients with both pretreatment and predischarge studies analyzable. Regional wall motion in the infarct site was measured by the centerline method and expressed in units of standard deviations (SDs) from the mean motion in 52 normal subjects. Patients treated with rt-PA (n = 77) achieved a significantly higher reperfusion rate after 90 min of treatment. Perfusion of the infarct-related artery improved from visual grade 0 or 1 (total occlusion or penetration without perfusion) to grade 2 or 3 (partial or full reperfusion) in 62% receiving rt-PA vs 31% receiving SK (n = 68) (p less than .001). However, the ejection fraction did not change significantly from before treatment to before discharge in either treatment group (+0.7 +/- 6.7% vs +1.0 +/- 8.3%, respectively). A small but significant increase in regional wall motion was observed in each of the two groups (+0.4 +/- 0.8 vs +0.3 +/- 0.8 SD/chord, respectively; each p less than .001 compared with baseline). This was countered by declines in the hyperkinesis of the noninfarct region (-0.3 +/- 1.0 SD/chord [p = .01] compared with baseline and -0.2 +/- 1.0 SD/chord [p = .23], respectively). Analysis of the combined groups revealed that the ejection fraction increased only in patients who achieved reperfusion by 90 min after onset of therapy or who had subtotal occlusions initially. There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery.

Cardiac Catheterization↗
PubMed1986

Advantages and applications of the centerline method for characterizing regional ventricular function.

We sought to identify theoretical advantages and applications of the centerline method for quantitative assessment of regional ventricular function. Motion was measured along 100 chords constructed perpendicular to a centerline drawn midway between the end-diastolic and end-systolic contours, and normalized for heart size. Abnormality was expressed in units of standard deviations from the mean motion in a normal reference population to indicate both the severity and significance of the wall motion abnormality. The mean abnormality averaged over 100 chords correlated highly with the area ejection fraction (r = .97). The centerline method uses a "sliding window" to measure motion where it is abnormal, because assessment of wall motion in predefined regions of the ventricular contour underestimates abnormality. From the 100 data points, the extent (% of contour) of regional abnormalities can also be determined. The severity of hypokinesis at the site of acute myocardial infarction correlated better with infarct size estimated from creatine kinase release (r = -.78) than did the ejection fraction or the circumferential extent of hypokinesis. Because the centerline method measures motion along locally determined vectors, and requires no apex, origin, coordinate system, or geometric reference figure, it can be applied to contours as dissimilar as the 60 degree left anterior oblique projection of the left ventricle and the 75 degree left anterior oblique projection of the right ventricle.

Computers↗
PubMed1986

Measurement of regional wall motion from biplane contrast ventriculograms: a comparison of the 30 degree right anterior oblique and 60 degree left anterior oblique projections in patients with acute myocardial infarction.

The value of performing biplane vs single plane analysis of regional wall motion from contrast ventriculograms was determined in 102 patients who received thrombolytic therapy and who underwent biplane ventriculography during acute myocardial infarction (n = 67), at follow-up more than 2 weeks later (n = 80), or both (n = 45). Hypokinesis in the infarct region and hyperkinesis in the noninfarct region were measured by the centerline method in the respective artery territories, which were defined from the data of 62 patients with single-vessel disease and were expressed in units of standard deviations from the mean of 32 normal subjects. Hypokinesis was more severe and extended over a longer segment of the left ventricular contour when measured in the right anterior oblique (RAO) projection in thrombosis of the left anterior descending coronary artery (LAD) but more severe and extensive in the left anterior oblique (LAO) projection in circumflex stenosis. Hyperkinesis opposite the LAD or the circumflex was greater in the LAO projection. In patients with thrombosis of the right coronary artery, wall motion abnormalities were similar in the two projections. Thus the evaluation of hypokinesis caused by acute coronary thrombosis and of the effect of therapeutic interventions in salvaging function can be adequately evaluated from single-plane 30 degree RAO ventriculograms, except in the small minority of patients with circumflex thrombosis.

Cineradiography↗
PubMed1985

Intravenous urokinase in acute myocardial infarction.

To achieve reperfusion early, an intravenous bolus of 2 million units of urokinase was administered in 50 patients with transmural acute myocardial infarction (AMI) 1.8 +/- 2.5 hours after the onset of symptoms. Coronary angiography performed 1.1 +/- 0.6 hours after urokinase therapy revealed patent coronary arteries in 30 patients (60%), with no significant difference between those with anterior and those with inferior AMI. Reocclusion occurred in only 1 of 24 patients restudied. Failure to achieve reperfusion was not related to the degree of systemic fibrinolytic activity, which was equally high in patients who did and those who did not achieve reperfusion, as evident from serially obtained fibrinogen measurements (77 +/- 52 vs 84 +/- 24 mg/dl, difference not significant). Plasmin activity, measured serially from 15 minutes to 24 hours after urokinase in 7 patients, was maximal at 15 minutes and undetectable after 3 hours. Wall motion at the infarct site measured from contrast ventriculograms was significantly better at follow-up only in patients in whom reperfusion was achieved and who received urokinase within 2 hours after the onset of symptoms as compared with patients in whom reperfusion was not achieved (-1.2 +/- 1.4 vs -2.4 +/- 0.9 standard deviations from normal, p less than 0.05). Peak serum creatine kinase level was significantly lower in patients in whom reperfusion was achieved than in those in whom it was not or those who had rethrombosis (802 +/- 763 vs 1,973 +/- 1,071 U/liter, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Time from onset of symptoms to thrombolytic therapy: a major determinant of myocardial salvage in patients with acute transmural infarction.

To determine whether myocardial salvage after successful intracoronary or intravenous thrombolysis is time dependent, the relation between left ventricular wall motion and the time to treatment was studied in 69 patients admitted less than 3 hours after onset of acute transmural myocardial infarction (42 patients with reperfusion by intracoronary streptokinase, 27 by intravenous urokinase). A similar significant relation between the time to treatment and the severity of regional hypokinesia at follow-up was found in the intracoronary and intravenous groups. To better define this relation, particularly during the early phase of infarction, the groups were combined. In patients in whom thrombolytic treatment was initiated within 2 hours after symptom onset, wall motion at follow-up was within 2 standard deviations of the normal mean in 82% (14 of 17 patients). If treatment was started 2 to 5 hours after symptom onset, the probability of improved wall motion decreased to 46% (24 of 52 patients, p less than 0.025). The time/wall motion relation appeared to be independent of infarct location, angiographically visible collateral vessels and the presence of subtotal coronary artery occlusion. The severity of hypokinesia at follow-up study correlated with the magnitude of peak serum creatine kinase (r = -0.71), indicating that thrombolytic therapy initiated within 2 hours after the onset of symptoms improves regional left ventricular function and reduces infarct size more than later therapy does.

Adolescent↗
PubMed1985

Factors that determine recovery of left ventricular function after thrombolysis in patients with acute myocardial infarction.

The coronary and ventricular angiograms of 47 patients with acute myocardial infarction in whom reperfusion was achieved by intracoronary streptokinase were quantitatively analyzed to determine the factors that affect recovery of regional left ventricular function after reperfusion. Hypokinesis in the infarct region was measured by the centerline method and expressed in terms of standard deviations (SDs) from normal. Severity of coronary artery stenosis was measured quantitatively. Hypokinesis showed more significant improvement after thrombolysis in patients with minimum stenosis diameter of greater than 0.4 mm than in those with severe residual stenosis, i.e., stenosis producing a minimum diameter of 0.4 mm or less (1.0 +/- 1.3 SD/chord, n = 31, vs 0.0 +/- 0.9 SD/chord, n = 7; p less than .05). Improvement in hypokinesis was greater in patients who received thrombolytic therapy within 2 hr than in those treated later (2.1 +/- 1.1, n = 8, vs 0.7 +/- 1.0 SD/chord, n = 28; p less than .001). These results indicate that angiographic reperfusion alone may not be sufficient: reperfusion must provide adequate flow and be achieved early to salvage myocardial function.

Adult↗
PubMed1985

Usefulness of coronary artery bypass graft surgery or percutaneous transluminal angioplasty after thrombolytic therapy.

Intracoronary streptokinase (STK) was given to 52 patients and 2 million U of intravenous urokinase was given to 15 patients with acute myocardial infarction less than 3 hr from onset of symptoms. Wall motion in the infarct region improved in 20 patients receiving STK alone (-2.5 +/- 1 to 2.1 +/- 1.1 SD/chord) and in 22 patients receiving STK and undergoing coronary bypass surgery within 24 hr (-2.5 +/- 1 to -1.5 +/- 1.0 SD/chord). Wall motion was unchanged in 10 patients not successfully reperfused with STK (-2.9 +/- 0.7 to -3.1 +/- 0.7 SD/chord). Regional wall motion improved at least 1.0 SD/chord in 71% of 14 patients treated within 2 hr of onset of symptoms, but in only 29% of 34 treated after 2 hr. Mean coronary artery stenosis after thrombolysis was 77 +/- 9%. Rethrombosis was associated with a stenotic cross-sectional area of less than 0.4 mm2. Ventricular function did not improve, with a residual stenosis of 0.4 mm or less in diameter. The Western Washington randomized trial reported a 1 year mortality of 2.5% in 80 successfully reperfused patients, but a mortality of 23% in 13 in whom reperfusion was partial and of 14.6% in 41 in whom reperfusion failed. The improved survival with successful reperfusion and improved ventricular performance with early and more complete reperfusion has stimulated interest in the need for angioplasty and coronary artery bypass grafting after thrombolytic therapy.

Angioplasty, Balloon↗
PubMed1983

Effect of interventions in salvaging left ventricular function in acute myocardial infarction: a study of intracoronary streptokinase.

The ability of intracoronary streptokinase (STK) infused early in acute myocardial infarction (MI) to salvage left ventricular (LV) function was studied in 52 patients who underwent contrast angiography immediately after STK and 6 +/- 7 weeks later. Ten nonrevascularized patients had no lysis or reocclusion. Of 42 patients with thrombolysis, 22 with optimal reperfusion underwent coronary artery bypass grafting (CABG) to prevent rethrombosis (STK + CABG group) and 20 did not (STK group). Motion was measured at 100 chords around the left ventricle and expressed in standard deviations (SD) from the normal mean. Hypokinesia was computed as the mean motion of chords in the infarct artery territory and hyperkinesia on the opposite wall was similarly computed. Hypokinesia improved greater than or equal to 1 SD/chord in 9 STK + CABG patients (41%), 8 STK patients (30%) (p = not significant versus STK + CABG) and 0 nonrevascularized patients. However, the ejection fraction did not change because it was normal in acute MI despite severe hypokinesia due to hyperkinesia on the opposite wall, and a subsequent decrease in hyperkinesia masked significant improvement in hypokinesia. It is concluded that regional wall motion must be measured to adequately assess the effect of therapeutic interventions on LV function. Early thrombolysis in acute MI results in improved LV function. The main benefit of CABG is to prevent rethrombosis.

Adult↗
PubMed1983

The effects of nitroglycerin-methoxamine combination on infarct size in conscious dogs.

The effect of nitroglycerin combined with methoxamine in reducing infarct weight was studied in conscious dogs. Ten minutes after permanent left anterior descending (LAD) coronary artery occlusion, 10 dogs received nitroglycerin (450 micrograms bolus IV, then 300 micrograms/min for 4 hours) and methoxamine as needed to maintain blood pressure and heart rate. No dogs in heart failure. Ten control dogs received saline solution. Dogs were sacrificed 3 days later. The region at risk of infarction was delineated by simultaneously perfusing the aortic root with Evans blue and the distal LAD artery with saline solution under equal pressures. Slices of stained hearts were incubated with tetrazolium to identify infarct. Total weight of left ventricle (LV), risk region, and infarct was measured. Nitroglycerin-treated dogs showed no difference from control dogs in infarct weight (26.2 +/- 5.9 gm +/- SE vs 27.7 +/- 5.6 gm), percent risk region/LV (36.0 +/- 1.4% vs 37.9 +/- 3.1%), or present infarct/LV (23.5 +/- 5.2% vs 24.8 +/- 4.9%). In a subgroup with risk region/LV less than or equal to 35%, nitroglycerin reduced infarct weight by 45% (8.8 +/- 8.5% vs 15.9 +/- 7.9%), percent infarct/LV by 49% (7.1 +/- 6.8% vs 13.8 +/- 6.6%), and percent infarct/risk region by 41% (23.0 +/- 22.0% vs 38.9 +/- 15.9%). Because of the small number of dogs in the study, differences were not significant. In dogs with risk region/LV greater than 35%, nitroglycerin had no effect. Thus, in dogs without overt heart failure, nitroglycerin may salvage ischemic tissue within small areas at risk of infarction, but the results are not definitive. However, our results clearly demonstrate that in the absence of failure, nitroglycerin does not reduce the size of large infarcts.

Animals↗
PubMed1983

Determinants of arrhythmic death during coronary artery reperfusion: effect of perfusion bed size.

To further our understanding of the factors determining the consequences of transient episodes of ischemia, we studied the influence of the size of the ischemic bed on the incidence of ventricular fibrillation (VF). The circumflex coronary artery (CFX) was occluded at various locations in 19 dogs. After 20 minutes of occlusion followed by 10 minutes of reperfusion the dogs were killed. The portion of the left ventricle (LV) at risk of infarcting (R/LV) was defined as the region supplied by the occluded CFX and determined by simultaneous perfusion of the CFX with saline solution, just beyond the occlusion site, and of the aorta with Evan's blue. Bread loaf slices of the heart were photographed and projected, and the normal (blue) and risk regions (unstained) traced. The product of area and slice weight yielded mass of normal and risk regions. The R/LV of dogs that died of reperfusion VF (n = 6) was 42.3 +/- 5.0%, larger (p less than 0.001) than R/LV in all surviving dogs (n = 13), 24.2 +/- 9.4%. Twelve of the 13 survivors had R/LV less than 35%, whereas all dogs that died had R/LV greater than 35% (p = 0.0005). As is true for VF occurring during coronary artery occlusion, the incidence of reperfusion VF is related to the size of the ischemic insult.

Animals↗
PubMed1983

Quantitative contrast angiography for assessment of ventricular performance in heart disease.

Contrast angiography provides much information about ventricular and valvular size and function. This review describes the calculation of left ventricular chamber volume and wall thickness and the derivation of ejection fraction, cardiac output, mass and wall tension and stress. In patients with valvular regurgitation, valve orifice area can be calculated by using the angiographic output and regurgitant flow determined by comparing the angiographic output with the cardiac output measured using Fick or indicator-dilution techniques. By analyzing ventricular volume in conjunction with pressure, it is possible to assess pressure-volume work, compliance and contractility. Regional wall motion can be measured from the change in ventricular contour with time. When applied clinically, these methods and measurements have been used to determine the hemodynamic characteristics of the compensated and decompensated left ventricle in valvular and coronary heart disease. The information derived from quantifying information in angiographic images contributes to patient diagnosis, assessment of prognosis and evaluation of therapy, and has added to our knowledge concerning the pathophysiology of heart disease.

Cardiac Volume↗
PubMed1983

Variability in the measurement of regional left ventricular wall motion from contrast angiograms.

Four types of variability affecting quantification of regional wall motion from contrast left ventriculograms (LVgrams) were studied. These included beat-to-beat variability in 24 LVgrams, intraobserver and interobserver variability in 20 LVgrams, and study-to-study variability in serial LVgrams of 21 patients with stable coronary artery disease. Motion was measured at 100 equidistant chords perpendicular to a center line drawn midway between the end-diastolic and end-systolic contours and normalized for heart size. Variability was computed as the absolute difference between observations. Beat-to-beat, intraobserver, and interobserver variability at the 100 chords were similar, averaging 14%, 14%, and 17%, respectively, of the mean motion in 64 patients with normal ventriculograms. Study-to-study variability was significantly higher, averaging 30% of mean normal motion, but was reduced when regional motion was calculated as the mean motion of chords within a region of interest. Variability peaked at the apex. Realignment to correct for cardiac rotation significantly increased variability. Investigators whose methods of wall motion analysis rely on identification of the apex as a landmark should be aware of this source of potential variability and error.

Arterial Occlusive Diseases↗
PubMed1983

Value of partial ejection fraction, volume increment, and regional wall motion in identifying patients with clinically significant coronary artery disease.

Recent studies suggest that the partial ejection fraction (EF) in early systole is a more sensitive index of left ventricular (LV) dysfunction than the holosystolic EF. We examined LV volume, partial EF, and volume increment at each of 12 time points in systole to determine which parameter best distinguishes normal subjects from patients with coronary artery disease (CAD). Contrast ventriculograms, obtained either in the right anterior oblique projection (60 frames/sec) or in the biplane projection (30 frames/sec), of 58 normal subjects and 68 patients with CAD were studied. The endocardial contour in each frame of a sinus beat was traced to derive a volume curve. At each twelfth of systole, LV volume was extrapolated from the curve and the partial EF was calculated. The increment in volume between successive time points was also calculated. Both partial EF and LV volume in patients with CAD became progressively more abnormal with time; peak abnormality occurred at end-systole. In a subgroup of patients with CAD who had normal holosystolic EF, both partial EF and volume were normal throughout systole. The increment in volume with each twelfth of systole in patients with CAD deviated less than 1 SD from normal throughout systole. Thus, maximum abnormality in partial EF and volume occurs at end-systole. Of the parameters of global LV function tested, holosystolic EF best distinguishes patients with CAD from normal subjects. However, regional wall motion measured in the area of interest is more sensitive to localized abnormality, the severity of which may be overestimated or underestimated by the EF due to hyperkinesis or hypokinesis in other regions of the left ventricle.

Cardiac Catheterization↗
PubMed1982

Effects of calcium channel blocking agents on reperfusion arrhythmias.

The effect of the calcium antagonists nifedipine (NF) and diltiazem (DT) on reperfusion after release of circumflex coronary artery (CX) occlusion was studied in open-chest dogs. Dogs were randomized to receive a bolus of 5 micrograms/kg NF (seven dogs), 1 microgram/kg NF (nine dogs), or vehicle (nine dogs). After bolus, high and low dose NF dogs were infused with 1 microgram/kg/min NF. All dogs then underwent 30 minutes CX occlusion followed by reperfusion. Dogs that did not develop ventricular fibrillation (VF) in the first 10 minutes of reperfusion were considered survivors. NF caused a dose-related increase in CX blood flow and decrease in mean arterial pressure (MAP), significant at the higher dose. Reperfusion VF occurred in five of nine low dose NF dogs, five of seven high dose NF dogs, and five of nine controls. Another 21 dogs were randomized to receive a bolus of 0.2 mg/kg DT (11 dogs) or vehicle (10 dogs). Infusion rates (and an additional bolus injection, if necessary) were chosen to produce a 10 to 20 mm Hg drop in MAP. CX occlusion and reperfusion were performed as above. Reperfusion VF occurred in 9 of 11 DT dogs vs 8 of 10 controls. Thus neither nifedipine nor diltiazem enhanced survival during reperfusion of myocardium previously subjected to 30 minutes of ischemia.

Animals↗
PubMed1982

Determinants of arrhythmic death due to coronary spasm: effect of preexisting coronary artery stenosis on the incidence of reperfusion arrhythmia.

Coronary spasm can occur in the presence or absence of coronary artery disease. We therefore determined the effect of preexisting coronary stenosis on the incidence of ventricular fibrillation during reperfusion after circumflex artery (CFX) occlusion. Twenty dogs underwent a 30-minute open-chest CFX occlusion. During reperfusion, CFX blood flow was restricted by a partial occluder. In dogs that survived reperfusion, peak CFX flow was 91 +/- 44% of baseline (mean +/- SD) compared with 163 +/- 68% in dogs that died of ventricular fibrillation (p less than 0.02). In another 17 dogs, the left anterior descending coronary artery was gradually occluded by an ameroid constrictor. After 17-39 days, the CFX was acutely occluded for 30 minutes and then reperfused. Collateral flow to the CFX, measured by microspheres, was 27.6 +/- 28.3 ml/min . 100 g-1 in dogs that died of reperfusion ventricular fibrillation, compared with 64.4 +/- 27.2 ml/min . 100 g-1 in surviving dogs (p less than 0.02). Thus, the risk of reperfusion ventricular fibrillation is greater in dogs with normal coronary arteries than in dogs with a flow-limiting partial stenosis of the artery undergoing transient occlusion, or chronic stenosis of a second coronary artery inducing collateralization to the artery subsequently undergoing transient occlusion. These results suggest that the risk of ventricular fibrillation during release of coronary spasm may be greater in patients without than in those with coronary artery disease.

Animals↗
PubMed1981

Lack of effect of aspirin on myocardial infarct size in the dog.

Pretreatment with platelet-inhibitory doses of aspirin (3 mg/kg body weight) has been shown to augment epicardial collateral flow by more than 50 percent (p less than 0.05) 4 hours after ligation of the left anterior descending coronary artery in dogs. To determine whether this favorable influence of aspirin is sufficient to decrease the amount of infarcted tissue, either intravenous aspirin, 3 mg/kg (n = 17), or saline solution (n = 17) was administered to dogs 10 minutes before occlusion of the left anterior descending coronary artery. Administration of saline solution or aspirin was repeated every 24 hours. By 72 hours, 5 dogs in each treatment group had died. Survivors were killed at 72 hours. The portion of the left ventricle at risk of infarction was delineated by perfusion of the aortic root with Evans blue and simultaneous perfusion of the distal left anterior descending coronary artery with saline solution under equal physiologic pressures. Slices of the stained heart were incubated with triphenyltetrazolium to identify gross infarct (with histologic confirmation). Total mass of left ventricle, myocardium at risk, and infarct size were measured in each dog. A direct relation was found between the mass at risk and the mass infarcted (r = 0.84, p less than 0.001). Aspirin-treated dogs did not differ from control dogs in percent ventricle at risk (mean +/- standard error 37 +/- 2 versus 40 +/- 2), percent infarct weight/left ventricle (29 +/- 3 versus 31 +/- 2) or percent infarct weight/weight of ventricle at risk (78 +/- 4 versus 77 +/- 3). Thus, despite aspirin's ability to inhibit platelet aggregation and to increase epicardial collateral flow by more than 50 percent, aspirin treatment failed to reduce infarct size in this dog model.

Animals↗