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M Hollenberg

Publications and source records attributed to M Hollenberg.

At least 37 records · Page 2Linked to original sources

Isoflurane anesthesia and myocardial ischemia: comparative risk versus sufentanil anesthesia in patients undergoing coronary artery bypass graft surgery. The SPI (Study of Perioperative Ischemia) Research Group.

Whether isoflurane has the potential to produce coronary artery steal and associated myocardial ischemia is still controversial. Previous studies addressing this issue in humans did not purposefully control hemodynamics or use continuous measures of myocardial ischemia. The authors used transesophageal echocardiography (TEE) and continuous Holter electrocardiography (ECG) to study the relative risk of myocardial ischemia during isoflurane or sufentanil anesthesia under strict control of hemodynamics in 186 high-risk patients undergoing elective coronary artery bypass graft (CABG) surgery. Overall, hemodynamics were well controlled (increased heart rate = 9.8%; increased systolic blood pressure = 7.1%; decreased systolic blood pressure = 10.8% of total prebypass time compared with preoperative baseline values), with no difference between the two anesthetics. In the 162 patients with interpretable TEE recordings, moderate to severe TEE ischemic episodes (grade change greater than or equal to 2) developed in 33 (21%) during the prebypass period, with no difference between isoflurane (12 of 56 = 21%) and sufentanil (21 of 106 = 20%) (P = 0.97). The duration and severity of TEE episodes were not significantly different between the two groups. No correlation was observed between TEE ischemic episodes and isoflurane concentrations (range 0.47-1.75%). In the 181 patients with interpretable ECG recordings, ECG evidence of ischemia developed in 34 (19%) during the prebypass period, with no difference between isoflurane (12 of 59 = 20%) and sufentanil (22 of 122 = 18%) (P = 0.87). The duration and severity of electrocardiographic ischemic episodes were also similar in patients receiving either isoflurane or sufentanil. Four of the 62 patients (6%) who received isoflurane had an adverse cardiac outcome versus 15 of 124 patients (12%) who received sufentanil (P = 0.34). The authors' findings demonstrate that, when hemodynamics are controlled, the incidence of myocardial ischemia (TEE or ECG) during isoflurane and sufentanil anesthesia is similar.

Adult↗

Physiological assessment of sensitivity of noninvasive testing for coronary artery disease.

The sensitivity of three noninvasive tests for coronary artery disease was assessed by means of quantitative indexes of disease severity in three different groups of patients. The overall population consisted of 110 subjects with limited coronary artery disease and no myocardial infarction. Planar dipyridamole-201Tl scintigraphy was evaluated in 31 patients, computer-assisted exercise treadmill in 28, and high-dose dipyridamole echocardiography testing in 51. Sensitivity was assessed by rigorous gold standards to define disease severity, such as measurement of minimum cross-sectional area and percent area of stenosis, by quantitative computerized coronary angiography (Brown/Dodge method). On the basis of the results of previous studies, the presence of physiologically significant coronary artery disease was indicated by a stenotic minimum cross-sectional area (MCSA) of less than 2.0 mm2 or a greater than 75% area of stenosis. With MCSA as the gold standard, dipyridamole-201Tl scintigraphy, computerized exercise treadmill, and dipyridamole echocardiography testing showed sensitivities of 52%, 54%, and 61%, respectively, in the three different patient cohorts enrolled. With percent area of stenosis as the gold standard, the sensitivity figures obtained for dipyridamole-201Tl, computerized exercise treadmill, and dipyridamole echocardiography testing were 64%, 54%, and 69%, respectively. For each of the three tests, sensitivity increased with increasing lesion severity. Sensitivity was also better in patients with left anterior descending coronary (LAD) disease when compared with patients with left circumflex or right coronary artery disease. Results of these studies, which were obtained with more strict patient selection criteria and by more rigorous gold standards than previous studies, demonstrate that in patients with limited coronary artery disease none of the tests evaluated is definitely superior in sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group.

BACKGROUND: Adverse cardiac events are a major cause of morbidity and mortality after noncardiac surgery. It is necessary to determine the predictors of these outcomes in order to focus efforts on prevention and treatment. Patients undergoing noncardiac surgery sometimes have postoperative cardiac events. It would be helpful to know which patients are at highest risk. METHODS: We prospectively studied 474 men with coronary artery disease (243) or at high risk for it (231) who were undergoing elective noncardiac surgery. We gathered historical, clinical, laboratory, and physiologic data during hospitalization and for 6 to 24 months after surgery. Myocardial ischemia was assessed by continuous electrocardiographic monitoring, beginning two days before surgery and continuing for two days after. RESULTS: Eighty-three patients (18 percent) had postoperative cardiac events in the hospital that were classified as ischemic events (cardiac death, myocardial infarction, or unstable angina) (15 patients), congestive heart failure (30), or ventricular tachycardia (38). Postoperative myocardial ischemia occurred in 41 percent of the monitored patients and was associated with a 2.8-fold increase in the odds of all adverse cardiac outcomes (95 percent confidence interval, 1.6 to 4.9; P less than 0.0002) and a 9.2-fold increase in the odds of an ischemic event (95 percent confidence interval, 2.0 to 42.0; P less than 0.004). Multivariate analysis showed no other clinical, historical, or perioperative variable to be independently associated with ischemic events, including cardiac-risk index, a history of previous myocardial infarction or congestive heart failure, or the occurrence of ischemia before or during surgery. CONCLUSIONS: In high-risk patients undergoing noncardiac surgery, early postoperative myocardial ischemia is an important correlate of adverse cardiac outcomes.

Adult↗

The "natural history" of segmental wall motion abnormalities in patients undergoing noncardiac surgery. S.P.I. Research Group.

Intraoperative segmental wall motion abnormalities (SWMA) detected by transesophageal echocardiography (TEE) are sensitive, but not always specific, markers of myocardial ischemia. To determine their incidence, characteristics, and relation to postoperative cardiac morbidity, we continuously recorded the left ventricular short-axis view and 12-lead ECG in 156 high-risk patients undergoing non-cardiac surgery. Monitoring was clinically blinded. Wall motion was scored at predefined clinical, hemodynamic, and ECG events and at periodic intervals (26 +/- 11 samples per patient). We detected 44 episodes of new or worsened SWMA in 32 patients (20%). The severity of most episodes was limited to severe hypokinesis (24/44, 55%) followed by akinesis (16/44, 36%) and dyskinesis (4/44, 9%). The remaining 124 patients had normal wall motion or only mild hypokinesis (56/156, 36%) or chronic SWMA (68/156, 44%). The incidence of new SWMA did not differ for patients with known coronary artery disease (CAD) and those with cardiac risk factors only (22% vs. 19%, P = not significant), although CAD patients had a significantly greater incidence of chronic SWMA (62% vs. 41%, P = 0.02). The incidence of new or worsened SWMA was significantly greater during aortic vascular surgery (38% vs. 17%, P = 0.05). Approximately 40% of all new TEE changes occurred in the absence of either an apparent clinical event or a significant change in systolic blood pressure or heart rate. Ten patients had new or worsened SWMA persisting until the end of surgery, 8 with new akinesis, only 1 developing myocardial infarction. The distribution of new or worsened SWMA and significant intraoperative ST-T changes (n = 19) in this cohort was discordant: temporal overlap between modalities was present in only 5 patients. Major cardiac complications occurred in 5 patients (3.2%), all of whom underwent peripheral vascularization. All patients with cardiac complications and new or worsened SWMA also had intraoperative or early postoperative ST-T changes. We conclude that: 1) continuous TEE recording with offline analysis in this high-risk group of patients revealed a relatively low incidence of new or worsened SWMA (20%), most episodes of which were characterized by severe hypokinesis (55%); 2) episodes were more common in patients undergoing aortic vascular surgery; 3) approximately 40% of episodes were unaccompanied by clinical events or significant hemodynamic changes; 4) episodes were poorly correlated with postoperative cardiac complications; and 5) the discordant relation between TEE and ECG changes observed here necessitates careful monitoring of the ECG when TEE is used clinically.

Aged↗

Usefulness of thallium-201 scintigraphy in predicting the development of angina pectoris in hypertensive patients with left ventricular hypertrophy.

Hypertension and left ventricular (LV) hypertrophy are independent risk factors for the development of coronary artery disease. To determine whether patients at higher risk for coronary artery disease can be identified, 40 asymptomatic hypertensive men with LV hypertrophy were prospectively studied using exercise thallium-201 scintigraphy and exercise radionuclide angiography. Endpoints indicative of coronary artery disease were defined as the subsequent development of typical angina pectoris, which occurred in 8 patients during a median follow-up of 38 months, or myocardial infarction, which did not occur. The exercise electrocardiogram was interpreted by standard ST-segment criteria and by a computerized treadmill exercise score. Abnormal ST-segment responses were present in 16 of the 40 hypertensives (40%), whereas the treadmill score was positive in 8 of those same 40 patients (20%). Scintigraphic perfusion defects assessed both visually and semiquantitatively were observed in 8 of 40 (20%) patients. An abnormal ejection fraction response to exercise was present in 40% (16 of 40) of patients, and 3 of 40 (7.5%) developed new wall motion abnormalities during exercise. Six of 8 patients with either perfusion defects or abnormal treadmill score developed typical angina during follow-up. All 5 patients with concordant positive exercise scintigrams and treadmill score developed chest pain during follow-up and had coronary artery disease confirmed by coronary angiography. However, only 7 of 16 (44%) patients with positive ST changes or abnormal ejection fraction responses during exercise developed chest pain during follow-up. In contrast, of 32 patients with negative scintigrams only 2 developed atypical chest pain syndromes, and significant coronary artery disease was excluded by angiography in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial ischemia in patients awaiting coronary artery bypass grafting.

The results of ambulatory ECG monitoring are described in a group of patients that have not previously been characterized. Fifty men who were initially seen for elective CABG surgery underwent 48 hours of continuous ambulatory ECG monitoring. ST segment deviation from baseline, trended every 15 seconds, was quantified for duration, maximum ST segment change, area under the ST segment-time curve (AUC), and average ST segment change for the episode (AUC/duration). Ischemic episodes, 87% of which were silent, occurred in 42% of the patients. Symptomatic episodes had greater maximum ST segment change than silent episodes (-2.4 vs -1.9 mm; p less than 0.05) but were shorter in duration (11 vs 18 minutes; p less than 0.05). Episodes that were unrelated to heart rate, that is, episodes with less than 20% increase in heart rate over the baseline rate at the onset of ischemia, made up 75% of all ischemic events and occurred in 90% of patients (19 of 21). Heart rate-related and unrelated ischemic episodes did not differ in duration, maximum ST segment change, AUC, or average ST segment change. It was concluded that: (1) as with patients with unstable angina, patients with severe coronary artery disease continue to have frequent episodes of silent myocardial ischemia despite intensive medical therapy; (2) painful episodes have greater maximum ST segment change but are shorter than silent ones; (3) most ischemic episodes (75%) occur without an initial increase in heart rate; and (4) heart rate-related and unrelated episodes are quantitatively similar.

Coronary Artery Bypass↗

Prognostic importance of postbypass regional wall-motion abnormalities in patients undergoing coronary artery bypass graft surgery. SPI Research Group.

Regional wall motion abnormalities (RWMA) detected by intraoperative transesophageal echocardiography (TEE) are thought to be sensitive markers of myocardial ischemia. To assess the prognostic significance of RWMA as compared with other less costly technologies such as electrocardiography (ECG) and hemodynamic measurements [blood pressure (BP) and pulmonary artery (PA) pressure], 50 patients were prospectively studied who were undergoing elective coronary artery bypass graft (CABG) surgery using continuous TEE, ECG (Holter), and hemodynamic measurements during the prebypass, postbypass, and early postoperative intensive care unit (ICU) periods (first 4 h). Echocardiographic and ECG evidence of ischemia was characterized during each of these three periods and related to adverse clinical outcomes (postoperative myocardial infarction, ventricular failure, and cardiac death). Clinicians were blinded to the TEE and ECG information. The prevalence of myocardial ischemia during the perioperative periods was as follows: prebypass, 20% (TEE) versus 7% (ECG); postbypass, 36% (TEE) versus 25% (ECG); ICU 25% (TEE) versus 16% (ECG). Neither prebypass TEE ischemia nor ECG ischemia occurring in any of the three periods predicted adverse outcome. In contrast, postbypass TEE ischemia was predictive of outcome: six of 18 patients with postbypass TEE ischemia had adverse outcomes versus 0 of 32 without TEE ischemia (P = 0.001). Seventy-three percent of the echocardiographic ischemic episodes occurred without acute change (+/- 20% of control) in heart rate, BP, or PA pressure. The authors conclude that: 1) prebypass myocardial ischemia was relatively uncommon, 2) the incidence of ECG and TEE ischemia was highest in the postbypass period, and 3) postbypass RWMA were related to adverse clinical outcome.

Adult↗

Perioperative myocardial ischemia: importance of the preoperative ischemic pattern.

Previous studies investigating the incidence of myocardial ischemia in patients undergoing coronary-artery bypass grafting (CABG) surgery have not considered the potential significance of the preoperative ischemic pattern in the development of intra- and postoperative myocardial ischemia and infarction. Accordingly, the authors compared the frequency and severity of pre-, intra-, and postoperative ischemic episodes (ST-segment depression greater than or equal to 0.1 mV or elevation greater than or equal to 0.2 mV) in 50 men with severe coronary artery disease scheduled for elective CABG. All subjects were monitored by continuous electrocardiography (ECG) (Holter monitor) for 2 preoperative days, intraoperatively, and 2 postoperative days (total monitoring time = 4,363 h). Routine anti-anginal medications were continued until the morning of surgery, and the anesthetic management of the patient was not controlled. During the preoperative period, 42% of the patients had ECG ischemic episodes, 87% of which were clinically silent. Only 18% developed intraoperative ischemia. Postoperatively, the incidence increased to 40%. The number of ischemic episodes/hour (epis/h) of monitoring among the three monitoring periods was similar (0.09 +/- 0.12 epis/h preoperatively, 0.11 +/- 0.20 epis/h intraoperatively, and 0.05 +/- 0.08 epis/h postoperatively; P = NS). The median duration of ischemic episodes was similar pre- and intraoperatively (16 vs. 18.5 min, P = NS), but greater postoperatively (41 min, P less than 0.05). Seventy-six per cent of the perioperative ECG ischemia occurred without acute change (+/- 20% of control) in blood pressure or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intraoperative myocardial ischemia: localization by continuous 12-lead electrocardiography.

Based primarily on results obtained during exercise treadmill testing, electrocardiographic (ECG) leads II and V5 are the suggested optimal leads for detecting intraoperative myocardial ischemia. However, these recommendations have not been validated in this setting using all 12 ECG leads. Accordingly, the authors studied 105 patients with known or suspected coronary artery disease (CAD) undergoing noncardiac surgery with general anesthesia by continuously recording the 12-lead ECG intraoperatively in all patients. The average duration of monitoring was 8.2 +/- 2.7 h (mean +/- SD). Ischemic episodes (i.e., greater than or equal to 1-mm horizontal or downsloping ST depression, greater than or equal to 1.5-mm slowly upsloping ST depression or greater than or equal to 1.5-mm ST elevation in a non-Q wave lead) occurred in 25 patients (24%). Out of 51 ischemic episodes, 45 involved ST depression alone, and the remaining six involved both ST depression and elevation. ST segment changes occurred in a single lead only in 14 episodes, while multiple leads were involved in 37 episodes. Lead sensitivity was estimated assuming that all ST segment changes were true positive responses. Sensitivity using a single lead was greatest in V5 (75%) and V4 (61%), and intermediate in II, V3, and V6 (33%, 24%, and 37%, respectively). The remaining seven leads demonstrated very low sensitivity (2-14%) or exhibited no ischemic changes (I and a VL). Combining leads V4 and V5 increased sensitivity to 90%, while the standard clinical combination, II and V5, was only 80% sensitive. Sensitivity increased to 96% by combining II, V4, and V5. The further addition of V2 and V3 (five leads) increased sensitivity to 100%. This study confirms previous recommendations for the routine use of a V5 lead (either uni- or bipolar) in all patients at risk for ischemia. V4 is more sensitive than lead II, and should be considered as a second choice. However, lead II, superior for detection of atrial dysrhythmias, is more easily obtained with conventional monitors. The use of all three would appear to be the optimal arrangement for most clinical needs, and is recommended if the clinician has the capability.

Aged↗

Systemic hypertension, left ventricular hypertrophy and coronary artery disease.

The potential mechanisms for the development of myocardial ischemia in hypertensive left ventricular (LV) hypertrophy involve changes in the coronary circulation characterized by a reduction of coronary vascular reserve and an acceleration of the atherosclerotic process. This combination of factors is probably reflected in the epidemiologic findings of increased coronary morbidity and mortality in hypertension, particularly when it is associated with LV hypertrophy. The failure of several antihypertensive trials to reduce coronary morbidity and mortality emphasizes the importance of early detection of significant coronary artery disease (CAD) among hypertensive patients with LV hypertrophy. A strategy to detect asymptomatic CAD based on combined probability of 2 noninvasive tests is discussed. Results obtained in hypertensive LV hypertrophy showed a 20% to 30% incidence of abnormal exercise test results, and these positive findings were predictive for the development of typical angina during a 3-year follow-up. Based on these results and reported data, it is extrapolated that patients with silent ischemia may contribute up to 40% of the coronary mortality observed in previous antihypertensive trials. These findings suggest the need for an early detection and separate follow-up of these patients with silent CAD, to better assess the influence of antihypertensive treatment on coronary morbidity and mortality.

Animals↗

Effect of epidermal growth factor on growth and postnatal development of the rabbit liver.

The effect of epidermal growth factor (EGF) on the postnatal development of the liver was examined. New Zealand White rabbits received 40 micrograms.kg-1.day-1 EGF from days 3 to 17 of age either intraperitoneally or orogastrically, whereas controls received saline. At days 18-20, animals underwent cannulation of the common duct using halothane anesthetic. Biliary output was measured directly for three 1-h periods: under basal conditions and in response to intravenous infusion of exogenous glycodeoxycholic acid at 0.75 and 1.5 mumol.min-1.kg-1, respectively. The bile salt pool size was measured by isotope dilution. Final mean body weight of intraperitoneal and orogastric groups did not differ from controls. Liver we weight, DNA, and protein content were significantly increased in intraperitoneally treated animals without morphological or biochemical evidence of fat deposition. Both intraperitoneal and orogastric EGF significantly increased bile salt secretion in the basal period and as a response to exogenous bile acid infusion. Bile flow was significantly increased in response to 1.5 mumol.min-1.kg-1 infusion of glycodeoxycholic acid. The bile salt pool was increased by both intraperitoneal and orogastric EGF. Administration of EGF resulted in a precocious development of glucokinase (EC 2.7.1.2) activity in the liver. EGF had no effect on serum cortisol, corticosterone, triiodothyronine, thyroxine, or free thyroxine levels. These findings suggest that in the neonatal period EGF can promote hepatic growth and maturation.

Animals↗

Comparison of a quantitative treadmill exercise score with standard electrocardiographic criteria in screening asymptomatic young men for coronary artery disease.

A computer-derived treadmill exercise score that quantifies the electrocardiographic response to exercise has been reported to have a high sensitivity (87 per cent) and specificity (92 per cent) in patients with a high prevalence of coronary artery disease. To test its accuracy in young, asymptomatic men with a low prevalence of coronary artery disease, we evaluated the responses of 377 military officers (mean age, 36.6 years) by two independent methods. According to standard electrocardiographic criteria, 45 of the subjects (12 per cent) had positive tests, whereas the treadmill exercise score indicated that only 3 (less than 1 per cent) had positive tests. Since two of these three had left ventricular hypertrophy and met only the criteria for the latter without associated coronary artery disease, the treadmill exercise score predicted that only 1 of 377 subjects would have clinically important coronary artery disease. Coronary arteriography, performed in 10 persons with the most positive scores on standard treadmill tests and the highest scores for risk factors, showed that nine subjects did not have coronary artery disease and that one had single-vessel disease (the same subject who the treadmill score predicted would have mild disease). The treadmill exercise score appears to improve the diagnostic specificity of exercise electrocardiography and may be more useful than values on standard stress tests in screening asymptomatic populations for coronary artery disease.

Adult↗

Influence of R-wave amplitude on exercise-induced ST depression: need for a "gain factor" correction when interpreting stress electrocardiograms.

Does 2 mm of ST depression induced by exercise have the same clinical significance in a patient with a 30-mm R wave as a patient with a 10-mm R wave in the same monitored lead? To answer this question the exercise responses of 85 patients were compared by 2 quantitative methods of assessing myocardial ischemia. A computer-derived treadmill exercise score, based largely on the characteristics of exercise-induced ST-segment depression, was compared with a thallium exercise score. Both scores correlated well over a wide range of values (r = 0.71, p less than 0.001). Then, the treadmill exercise score was corrected (by adjusting the magnitude of the ST depression to a standardized R-wave amplitude of 12 mm in V5 and 8 mm in aVF) to determine if this would improve its correlation with the thallium exercise score. The patients were separated into 2 groups by R-wave amplitude: 53 had an RV5 of 9 to 17 mm and 32 had an RV5 less than 9 or greater than 17 mm. Correction of the treadmill exercise score for R-wave amplitude did not change the slope and intercepts of the regression line for patients with an RV5 amplitude of 9 to 17 mm, but did for those with an RV5 amplitude less than 9 or greater than 17 mm. In this latter group, R-wave correction changed the regression line from one that differed significantly from that of patients with less extreme RV5 voltage to one that was indistinguishable from it. Correction of the treadmill exercise score also increased the correlation coefficient from 0.54 to 0.68 in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Effect of epidermal growth factor on ontogeny of the gastrointestinal tract.

The effect of epidermal growth factor (EGF) on the ontogeny of the gastrointestinal tract was examined in New Zealand White rabbits. EGF, 40 micrograms X kg-1 X day-1, was administered to suckling animals from 3-18 days of age either intraperitoneally or orogastrically. Controls received saline. Animals were killed at 17-18 days of age. Body weight and wet weight of stomach, pancreas, and 10-cm segments of proximal, mid, and distal small intestine were measured. The total pancreas was homogenized for determination of protein, DNA, and amylase, and the intestinal mucosa was scraped, weighed, and homogenized for estimation of protein, DNA, sucrase, and lactase. While body weights were similar wet weight of stomach and pancreas were increased by intraperitoneal and orogastric EGF. Small intestinal wet weights were increased in all segments by intraperitoneal but not orogastric EGF, and both routes significantly increased mucosal DNA in the distal segment. EGF administered orogastrically induced precocious maturation of intestinal brush-border disaccharidase activities but had no effect on pancreatic amylase, whereas EGF administered intraperitoneally induced precocious maturation of pancreatic amylase but had no effect on brush-border disaccharidase activities. These findings suggest that both systemic and oral EGF play a role in regulating growth and postnatal maturation of the gastrointestinal tract.

Amylases↗

Detection and quantification of previous myocardial infarction by exercise-redistribution tomographic thallium-201 scintigraphy.

Although myocardial perfusion scintigraphy at rest accurately diagnoses myocardial infarction (MI), the prevalence and size of previous MI is overestimated by exercise-redistribution thallium-201 studies. A new, quantitative approach to the analysis of tomographic thallium-201 scintigrams was developed in order to determine whether the presence and extent of MI could be determined. Sixty patients undergoing cardiac catheterization for chest pain syndromes, including 28 with previous MI, were studied by exercise and 3-hour delayed thallium-201 scintigraphy, with use of the 7-pinhole tomographic technique. Circumferential profiles of the postexercise and 3-hour radiotracer distribution were generated from apical, midventricular and basal left ventricular slices. The 3-hour profile fell below normal limits in 24 of 28 patients (86%) with remote MI, but was also abnormal in 9 of 22 patients (41%) with coronary disease but no MI. All missed MIs were either inferior or subendocardial and were associated with normal ejection fractions. To distinguish between MI and slowly resolving ischemic defects, a quantitative approach was used. MI area was calculated as the area in which the 3-hour profile fell below the 3-hour normal limits, and a redistribution area in the MI zone was determined as the area between the postexercise and 3-hour profiles in the region where the 3-hour profile was abnormal. The MI area was 1,000 +/- 980 units in patients with MI, vs 79 +/- 120 units in patients without MI (p less than 0.001), whereas the redistribution area was higher in patients without MI (1,240 +/- 810 vs 430 +/- 400 units, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improved efficacy of high-dose versus medium- and low-dose diltiazem therapy for chronic stable angina pectoris.

The efficacy of therapy with diltiazem, 360 mg/day, was studied in 11 men with chronic, stable angina pectoris. An initial dose-titration schedule in which diltiazem was increased weekly from placebo to 120, 240 and 360 mg/day (Period I) was followed by a randomized, double-blind, 1-month crossover trial of placebo vs diltiazem at 360 mg/day (Period II). A computer-assisted treadmill exercise test was performed at the end of each dose and each 2-week crossover period. Diltiazem at 360 mg/day, compared with placebo (Period II), significantly improved exercise performance. Exercise duration to onset of chest pain increased 40% from 5.3 +/- 2.1 to 7.4 +/- 2.7 minutes (p less than 0.01). Time to reach 1 mm of ST-segment depression increased 33%, from 5.1 +/- 2.0 to 6.8 +/- 1.8 minutes (p less than 0.01). Total exercise duration increased 16%, from 7.5 +/- 2.0 to 8.7 +/- 2.0 minutes (p less than 0.005). A computer-derived quantitative treadmill exercise score improved 27%, from -13.1 +/- 9.4 to -9.5 +/- 7.6 units (p less than 0.005), and the ST-segment depression at peak exercise improved from -1.9 +/- 1.1 to -1.6 +/- 1.2 mm (p less than 0.05). Progressive improvement in these variables was seen during the single-blind dose-titration period between 120 and 240 mg/day and between 240 and 360 mg/day (Period I). Baseline heart rate (HR) and diastolic blood pressure (BP) in the supine and upright position were significantly lower with diltiazem than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Clinical studies with transdermal nitroglycerin.

The short- and long-term effects of various Nitro-Dur formulations on performance and hemodynamics were studied in 15 men with stable angina pectoris who also had a positive treadmill exercise test. A treadmill exercise score (TES) was used that quantified the "ischemic" ST segment response to exercise. The score incorporated information that reflected the rapidity of evolution of ST segment depression during exercise and the time required for it to resolve after cessation of exercise. In early tests (n = 10) Nitro-Dur improved both the TES (by 31%: p less than 0.0001) and the time required for 1 mm ST segment depression (by 33%: p less than 0.0001). At all dosage levels, Nitro-Dur also decreased resting systolic blood pressure and increased resting heart rate. No dose-response patterns emerged. Changes in TES and time to ST segment depression were greater with sublingual nitroglycerin than they were with Nitro-Dur. In tests conducted after prolonged dosage (n = 5), the effects of Nitro-Dur on blood pressure and heart rate became attenuated at weeks 2 and 4, although cardiac responsiveness was preserved, as reflected in the increased time required before the occurrence of 1 mm ST segment depression. The latter effect was also observed with sublingual nitroglycerin. The clinical relevance of these data to the design of individual patient therapy is discussed.

Angina Pectoris↗