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Biomedical subjects

J Wynne

Publications and source records attributed to J Wynne.

At least 55 records · Page 3Linked to original sources

Addition of nifedipine to maximal beta-blocker-nitrate therapy: effects on exercise capacity and global left ventricular performance at rest and during exercise.

Nifedipine is a potent coronary vasodilator in the resting state and an effective afterload-reducing agent. This study was undertaken because of the concern that the addition of nifedipine to beta-blocker therapy could produce serious untoward hemodynamic consequences. Although this combination is usually well tolerated, occasional reports suggest that the combination of nifedipine and beta-blocking agents may increase the likelihood of congestive heart failure, severe hypotension or exacerbation of angina. Further, there is a need to know if the addition of nifedipine to therapy with maximally tolerated doses of long-acting nitrates and beta blockers would provide further symptomatic relief without excessive adverse effects. Finally, the effect of adjunctive nifedipine on global left ventricular performance at rest and during exercise was examined. Sixteen patients, all of whom had 3 or more episodes per week of angina pectoris despite therapy with long-acting nitrates and beta blockers, were selected. Radionuclide ventriculography was performed at rest and during exercise; global ejection fractions (EFs) were determined by manually tracing the left ventricular end-diastolic perimeter with an electronic cursor. In the first phase, beta blockers and nitrates were used; in the second phase nifedipine, 10 mg every 6 hours, was added and titrated to reduce systolic blood pressure at rest by at least 10 mm Hg or until intolerable adverse effects occurred. When nifedipine was added to therapy, the difference between global EF at rest and during exercise was reduced from - 0.15 to + 0.02 (p less than 0.00001); exercise duration was increased from 431 seconds to 532 (p less than 0.001), with only 8 patients limited by angina, compared with 16 during the initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Addition of nifedipine to maximal nitrate and beta-adrenoreceptor blocker therapy in coronary artery disease.

The effects of oral nifedipine on left ventricular (LV) diastolic function were assessed in 14 patients with coronary artery disease (CAD) who had symptoms despite therapy with beta-adrenoceptor blocking drugs and nitrates. Rest and exercise gated radionuclide ventriculography was performed before and a mean of 13 days after the addition of oral nifedipine (80 to 120 mg/day) to baseline medication. Ejection fraction did not increase in any patient during exercise. The addition of nifedipine slightly improved the LV ejection fraction response to exercise (control, 49 +/- 8% rest vs 44 +/- 9% exercise; nifedipine, 47 +/- 6% vs 48 +/- 8%). With nifedipine treatment, diastolic function improved, with a decrease in the time to peak filling rate (PFR) at rest (from 174 +/- 34 to 152 +/- 31 ms, p less than 0.005) and an increase in PFR with exercise (from 2.5 +/- 0.6 to 3.4 +/- 0.7 end-diastolic volume/s, p less than 0.0005). Using the ratio of PFR/peak ejection rate as a variable, preferential improvement of diastolic over systolic function occurred during exercise (1.03 +/- 0.29 baseline vs 1.4 +/- 0.43 with nifedipine, p less than 0.01). Duration of exercise increased by a mean of 21% with nifedipine (from 454 +/- 150 to 550 +/- 159 seconds, p less than 0.005); all 14 patients were limited by angina pectoris at baseline, whereas only 5 patients were limited by angina pectoris after nifedipine treatment. This study shows that global LV diastolic function is improved by oral nifedipine treatment both at rest and during exercise in patients on maximally tolerated doses of beta-adrenoreceptor blockers and nitrates, and is associated with improvement of symptoms and exercise tolerances.

Adrenergic beta-Antagonists↗

Relation between the transmural extent of acute myocardial infarction and associated myocardial contractility two weeks after infarction.

To characterize the relation between the transmural extent of acute myocardial infarction (AMI) and associated regional contractility after recovery from ischemia, 11 mongrel dogs underwent occlusion of the proximal left anterior descending coronary artery and were evaluated 2 weeks after infarction. Occlusion was permanent in 5 dogs, and reperfusion was allowed after 2 hours of occlusion in 6 dogs. All dogs had computer-assisted quantitative wall-thickening analysis by 2-dimensional echocardiography and infarct localization by the triphenyl-tetrazolium chloride technique. Percent systolic wall thickening was correlated with the transmural extent of AMI in 40 regions of interest, each measuring approximately 60 arc degrees in circumference. In 11 non-infarct-containing regions, the mean wall thickening was 59 +/- 16% (+/- standard deviation). In 29 infarct-containing segments (with transmural extent of infarction 11 to 100%) systolic wall thickening ranged from -4% to 47%. Wall thickening and transmural extent of AMI were inversely related. Least-squares regression analysis found the relation to be best described by the logarithmic function, percent wall thickening = 61 - 26 log (percent transmural extent of infarction +1), r = -0.87. The nature of this relation between structure and function suggests that salvage of small amounts of myocardium (transmural extent less than 30 to 40%) by coronary reperfusion or other means may have little effect on systolic myocardial function when compared with the function of transmural infarcts. Alternatively, salvage of more than 40% of the jeopardized myocardium should be expected to appreciably augment myocardial function.

Animals↗

Calcium channel blockers in congestive heart failure: theoretic considerations and clinical experience.

Although it has been suggested that calcium channel blocking agents may be utilized as vasodilators in patients with congestive heart failure, these agents also have the potential to cause a deterioration in cardiac function because of their negative inotropic actions. There is considerable variation among the available agents with regard to their relative effects on the vasculature, myocardial inotropy, and myocardial chronotropy. Thus, at clinically relevant dosages, nifedipine is a potent systemic and coronary vasodilator, but it has little or no direct effect on inotropy and chronotropy. In contrast, verapamil exerts significant negative inotropic and chronotropic effects at vasodilatory dosages, whereas diltiazem is a potent vasodilator with a negative chronotropic action at dosages that do not affect inotropy. In patients with heart failure, the largest experience so far has been with nifedipine. Data derived from over 100 patients with moderate to severe congestive heart failure indicate a generally beneficial net hemodynamic response to nifedipine, with substantial improvements in cardiac index (+24 percent) and left ventricular filling pressure (-15 percent). The major effect seems to be on arteriolar resistance vessels, resulting in a reduction in afterload, with relatively little effect on venous pressures. Limited data suggest that the initial effect is sustained during long-term therapy. The clinical experience with verapamil and diltiazem in patients with heart failure is at present limited. In patients with normal or mildly impaired left ventricular function, verapamil's vasodilator and negative inotropic effects are counterbalanced. With severe left ventricular dysfunction, however, treatment with verapamil can result in abrupt decompensation and development of overt pulmonary edema and hypotension. Diltiazem's relative lack of negative inotropic effects may allow it to be used safely in patients with congestive heart failure, particularly when control of supraventricular tachyarrhythmia is required.

Calcium↗

Proteolysis of ankyrin and of band 3 protein in chemically induced cell fusion. Ca2+ is not mandatory for fusion.

Human erythrocytes were fused by incubation with 0.5-2 mM-chlorpromazine hydrochloride at pH 6.8-7.6. Fusogenic preparations of chlorpromazine were cloudy suspensions of microdroplets, and below pH 6.8 chlorpromazine gave clear solutions that were inactive. Unlike control cells, the lateral mobility of the intramembranous particles of the PF-fracture face of chlorpromazine-treated cells was relatively unrestricted, since the particles were partly clustered at 37 degrees C and they exhibited extensive cold-induced clustering. Ca2+ stimulated fusion, but fusion was only very weakly inhibited by EGTA (10 mM) and by N-ethylmaleimide (50 mM); pretreatment of the cells with Tos-Lys-CH2Cl (7-amino-1-chloro-3-L-tosylamidoheptan-2-one) (7.5 mM) markedly inhibited fusion. Changes in the membrane proteins of erythrocytes fused by chlorpromazine, before and after treatment with chymotrypsin to remove band 3 protein, were investigated. The several observations made indicate that the Ca2+-insensitive component of fusion is associated with degradation of ankyrin (band 2.1 protein) to band 2.3-2.6 proteins and to smaller polypeptides by a serine proteinase that is inhibited by Tos-Lys-CH2Cl, and that the component of fusion inhibited by EGTA and N-ethylmaleimide is associated with degradation of band 3 protein to band 4.5 protein by a Ca2+-activated cysteine proteinase. Proteolysis of ankyrin appeared to be sufficient to permit the chlorpromazine-induced fusion of human erythrocytes, but fusion occurred more rapidly when band 3 protein was also degraded in the presence of Ca2+. Since other cells have structures comparable with the spectrin-actin skeleton of the erythrocyte membrane, the observations reported may be relevant to the initiation of naturally occurring fusion reactions in biomembranes. It is also suggested that, should polypeptides with fusogenic properties be produced from integral and skeletal membrane proteins by endogenous proteolysis, their formation would provide a general mechanism for the fusion of lipid bilayers in biomembrane fusion reactions.

Anion Exchange Protein 1, Erythrocyte↗

Response of reperfusion-salvaged, stunned myocardium to inotropic stimulation.

The purpose of this study was to determine whether myocardium salvaged by reperfusion following coronary occlusion could respond to inotropic stimulation by dopamine. Mongrel dogs underwent a 2-hour occlusion of the proximal left anterior descending coronary artery, followed by reperfusion for 5 or 28 hours. Dopamine (5 to 10 micrograms/kg/min) or dextrose was administered 1 hour or 24 hours after the onset of reperfusion. Serial, computer-assisted, two-dimensional echocardiographic determination of percentage of systolic wall thickening (%SWT) and cross-sectional ejection fraction (% delta area) were used to evaluate the response to treatment. Myocardium in the region of central ischemia contracted poorly after 1 hour of reperfusion (mean %SWT = 1.3 +/- 13.3% [mean +/- SD] compared to preocclusion value of 43.6 +/- 18.5%, p less than 0.001) and tended to thin at 24 hours of reperfusion (mean %SWT = -6.0 +/- 12.3%, p less than 0.001). After 1 hour of reperfusion, dopamine produced a greater than fourfold improvement in %SWT within the reperfused zone (to 15.3 +/- 7.3%, p less than 0.05). After 24 hours of reperfusion, dopamine again produced an improvement in %SWT (to 5.8 +/- 12.5%, p less than 0.05). There were no significant changes in %SWT with dextrose infusion. Thus, dopamine stimulates the reperfusion-salvaged but noncontracting (stunned) myocardium to contract as early as 1 hour after reperfusion.

Animals↗

Equilibrium (gated) radionuclide ejection fraction measurement in the pressure or volume overloaded right ventricle. Comparison of three methods.

Although equilibrium radionuclide angiographic measurement of right ventricular ejection fraction (RVEF) has been validated in patients with coronary artery disease, the accuracy of this technique has not been demonstrated in patients with other cardiac diseases which may result in RV pressure and/or volume overload. The accuracy of three methods of equilibrium radionuclide analysis for measuring RVEF was compared in several subgroups of patients with a variety of cardiac diseases, including congenital and valvular heart disease, cor pulmonale, and cardiomyopathy. It was concluded that RVEF may be accurately derived by equilibrium radionuclide ventriculography in patients with a wide variety of cardiac diseases, including those resulting in RV volume and/or pressure overload. Accuracy varies depending on analysis method and the nature of the hemodynamic derangement.

Adult↗

Quantitative analysis of left ventricular function: pre- and postischemic two-dimensional echocardiography in dogs.

A quantitative technique that aligns the diastolic and systolic silhouettes was used to assess left ventricular function (wall thickening and endocardial wall motion) from two-dimensional echocardiographic studies for every 2 degrees of arc of the left ventricular circumference in canines. Thirty-two dogs were studied before and at specific intervals up to 14 days after either temporary or permanent occlusion of the left anterior descending coronary artery. Decreased systolic wall thickening and frank systolic thinning were observed in the ischemic/infarcted region 90 min and 6 hr after occlusion; endocardial motion showed the abnormally contracting segment less clearly. Partial recovery was seen in both groups of animals but to a greater degree in those with temporary occlusion. The technique was useful for assessing sequential changes in wall motion.

Animals↗

Quantitative computer-assisted analysis of left ventricular wall thickening and motion by 2-dimensional echocardiography in acute myocardial infarction.

Quantitative regional wall motion analyses of 2-dimensional echocardiograms (2-D echo) have usually focused on large arcs (greater than 45 degrees) of the left ventricular (LV) perimeter rather than on small LV zones. Few studies have assessed changes in wall thickness. To determine normal ranges of regional LV function, the endocardial and epicardial contours of short-axis 2-D echoes obtained at the papillary muscle level of 10 normal subjects were manually traced. Then, 15 patients with acute myocardial infarction (MI) were studied, comparing their contours at admission with ranges determined from the normal subjects. In all patients with MI, 2-D echoes located abnormal wall motion involving at least the region identified as abnormal by the electrocardiogram and often extending into adjacent regions. All 9 patients with transmural MI had either decreased wall thickening or abnormal endocardial wall motion; all except 1 had focal thinning in the region of the MI. Of the 6 patients with nontransmural MI, 2 had abnormal endocardial wall motion, and all had decreased wall thickening. Evaluating regional wall motion at multiple points around the LV circumference should permit more precise delineation of LV function in health and disease than has been heretofore possible.

Adult↗

Improving diagnostic accuracy of the exercise test by combining R-wave changes with duration of ST segment depression in a simplified index.

To enhance the reliability of the exercise test in diagnosing both overall coronary artery disease and multivessel coronary artery disease, a discriminant function was obtained by means of stepwise linear discriminant analysis. Both electrocardiographic and nonelectrocardiographic factors were used to derive the discriminant function in a retrospective group of 231 patients, 168 of whom had angiographically defined coronary artery disease. The discriminant function converted into a simple exercise index or score was then applied to a retrospective group of 120 patients, 98 of whom had coronary artery disease. This index, combining R-wave changes with duration of ST segment depression and patient's sex, proved highly accurate in diagnosing coronary artery disease in male patients and in diagnosing the absence of coronary artery disease in female patients. When compared to standard ST segment criteria, the sensitivity and predictive value of the exercise index was significantly higher.

Adult↗

Noninvasive assessment of valvular heart disease: surgery without catheterization.

Forty-one patients underwent valve surgery at our institution based solely on clinical, M-mode echocardiographic, phonocardiographic, and external pulse recording findings without preoperative cardiac catheterization. Patients with clinical evidence of coronary artery disease were excluded from the study. Preoperatively, 83% of the patients were New York Heart Association functional class III or IV. In all patients, the noninvasive evaluation was considered sufficiently diagnostic of the nature and severity of valvular heart disease to allow surgery without preoperative catheterization. In 23 of 41 cases (group 1), cardiac catheterization was not performed due to the patients' unstable hemodynamic condition at the time surgery was being considered. In the remaining 18 patients (group 2), the probability of obtaining data at catheterization that would significantly affect management decisions was thought to be low, thus not justifying the cost and potential morbidity of this procedure. In all cases, the noninvasive diagnosis was corroborated at operation; there were no unexpected findings nor deaths related to incomplete or incorrect diagnoses. Over a followup period of 4.5 +/- 1.4 years, no patient experienced signs or symptoms of ischemic heart disease. In selected patients without anginal chest pain syndromes, appropriate and successful valve surgery may be performed on the basis of combined clinical and noninvasive evaluation without the need for cardiac catheterization.

Adolescent↗

Clinical utility and management impact of M-mode echocardiography.

To determine the clinical utility and management impact of M-mode echocardiography, 182 echocardiograms were analyzed at a university teaching hospital. The physicians who ordered the echocardiograms said that 12 percent provided crucial information that was not available from other tests and that 26 percent resulted in a change in patient management. According to two independent board-certified cardiologist-reviewers, 86 percent of echocardiograms were appropriately ordered, but only 15 echocardiograms (8 percent) were actually needed for a change to a new and appropriate management. According to the reviewers, the 77 Group I M-mode echocardiograms (those ordered to evaluate left ventricular function, left atrial size, potential cardiac sources of emboli, or the possibility of bacterial endocarditis, or those ordered in patients who, according to the ordering physician, had undergone or would undergo catheterization regardless of the results of echocardiography) were less likely than the 105 Group II M-mode echocardiograms (those ordered to evaluate possible mitral valve prolapse, hypertrophic cardiomyopathy, valvular function, or the pericardium) to be ordered appropriately, to provide helpful information, or to provide crucial results. Group I echocardiograms had reviewer-assessed appropriate management impact in only one case (1 percent) compared with a 13 percent rate of management impact for Group II M-mode echocardiograms (p less than 0.01). Although echocardiography can be accurate and valuable with yields similar to those of other noninvasive procedures, 77 (42 percent) of 182 M-mode echocardiograms in this hospital could be predicted at the time of ordering to be in a low-yield group.

Echocardiography↗

Quantitative analysis of left ventricular wall motion and thickness using two-dimensional echocardiography.

The real time two-dimensional ultrasonic imaging of the left ventricle made possible segmental echocardiographic measurements of wall motion and thickening and thinning. The underlying hypothesis is that measurements of regional wall motion could quantify the extent of myocardial ischemia and infarction; the method could be used as a truly non-invasive tool to assess the severity of damage from infarction and the effects of interventions designed to limit infarcts. The method is operator interactive. Each patient's data could be compared with data for a normal group. The selection criteria for the normal patients have been described. The confidence region of the normal group and the effect of averaging over three tracings for three heartbeats have been computed. Technical difficulties inherent in the method and possible improvements are discussed.

Computers↗

Prevention by nifedipine of cold pressor-induced decrease in left ventricular ejection fraction.

To examine the effects of nifedipine on changes in ventricular function produced by cold, the cold pressor test was administered to eight patients with angiographically documented coronary artery disease. Radionuclide ventriculograms were obtained at baseline and during the cold pressor stimulus both before and after administration of nifedipine, 10 mg buccally; thus, four serial radionuclide ventriculograms were obtained per patient. The cold pressor stimulus did not produce any significant difference in the mean (+/- standard deviation) peak rate-pressure product during the control or nifedipine test (10,900 +/- 3,390 versus 10,600 +/- 3,700). However, the increase in systolic blood pressure (p = 0.05) and the peak systolic blood pressure achieved (p less than 0.001) were greater during the control (134 +/- 19 to 160 +/- 25 mm Hg) than during the nifedipine (125 +/- 18 to 145 +/- 21 mm Hg) cold pressor test. The mean global left ventricular ejection fraction decreased during the control cold pressor test from a baseline value of 0.60 +/- 0.08 to 0.52 +/- 0.08 (p = 0.004). After nifedipine, this variable did not change during the repeat cold pressor test (0.63 +/- 0.09) compared with the repeat baseline value (0.63 +/- 0.11). Therefore, the difference in left ventricular ejection fraction response during control versus nifedipine cold pressor testing was highly significant (p less than 0.0001). In patients with obstructive coronary artery disease, nifedipine abolished the decrease in left ventricular ejection fraction observed during the control cold pressor test and may be of value to protect patients from cold-induced left ventricular dysfunction. The mechanism may be a combination of coronary artery vasodilation and systolic unloading of the left ventricle.

Adult↗

Right ventricular ejection fraction: an indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease.

The predictive value of radionuclide ventriculography was studied in 34 patients with depressed left ventricular ejection fraction (less than 40%) and clinically evident congestive heart failure secondary to atherosclerotic coronary artery disease. In addition to left ventricular ejection fraction, right ventricular ejection fraction and extent of left ventricular paradox were obtained in an attempt to identify a subgroup at increased risk of mortality during the ensuing months. The 16 patients who were alive after a 2 year follow-up period had a higher right ventricular ejection fraction and less extensive left ventricular dyskinesia. When a right ventricular ejection fraction of less than 35% was used as a discriminant, mortality was significantly greater among the 21 patients with a depressed right ventricular ejection fraction (71 versus 23%), a finding confirmed by a life table analysis. Depressed right ventricular function was further linked to more severely compromised left ventricular function, as confirmed by a greater reduction in left ventricular ejection fraction and by an increased extent of left ventricular dyskinesia. These patients had a greater prevalence of chronic obstructive pulmonary disease and previous inferior myocardial infarction but the differences between groups were not statistically significant. It appears that the multiple factors contributing to the reduction in right ventricular ejection fraction make it a useful index not only for assessing biventricular function, but also for predicting patient outcome.

Actuarial Analysis↗

Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia.

Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.

Angiography↗