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Biomedical subjects

J E Muller

Publications and source records attributed to J E Muller.

At least 73 records · Page 4Linked to original sources
PubMed1995

Requirements for controlled clinical trials of preoperative cardiovascular risk reduction.

Although controlled clinical trials have had a major impact in many areas of cardiovascular disease management, they have had little influence on preoperative cardiac risk reduction. Over the past 2 years, we have conducted the Reduction of Cardiac Operative Risk (RCOR) Trial, a pilot study designed to determine enrollment and event rates for a definitive trial evaluating a strategy to reduce cardiac risk associated with noncardiac surgery. This experience indicates that a successful, definitive trial will require recognition of the multiple questions to be answered, accurate identification of the study population, a large sample size, cooperation between internists, surgeons, and anesthesiologists, and strategies to minimize cost. The high costs and difficulties of such a trial are likely to be outweighed by the enormous benefit of identifying the proper strategy for the use of the expensive testing methods that are currently employed.

Cardiovascular Diseases↗
PubMed1995

Sequential combination thrombolytic therapy for acute myocardial infarction: results of the Pro-Urokinase and t-PA Enhancement of Thrombolysis (PATENT) Trial.

OBJECTIVES: The present study was designed to test the efficacy and safety of a sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction. BACKGROUND: Efforts continue to identify a thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-PA and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As a result, certain combinations of these activators have been found to be synergistic in vitro and in vivo. METHODS: In a multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and given a low dose bolus of rt-PA (5 to 10 mg) followed by a 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min. RESULTS: Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect a possible reocclusion. All 28 patients with a patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death. CONCLUSIONS: A sequential combination of low dose rt-PA and reduced-dose pro-urokinase produced a high TIMI 3 patency rate, was well tolerated and was associated with a low reocclusion rate.

Adult↗
PubMed1995

Triggering of acute myocardial infarction.

The mechanisms of acute coronary artery disease onset are receiving increasing attention. Study of these mechanisms has been stimulated by the finding that the onset of acute myocardial infarction is more likely during the morning hours after awakening, suggesting that activities of the patient often trigger the event. Triggering may occur when stressors placed on the body produce hemodynamic, vasoconstrictive, and prothrombotic forces-acute risk factors-that can cause disruption of a vulnerable atherosclerotic plaque leading to thrombosis. Insight into triggering and plaque vulnerability may lead to a new approach in the prevention of acute myocardial infarction.

Circadian Rhythm↗
PubMed1994

Hemodynamic and hemostatic responses to morning and evening exertion in systemic hypertension and implications for triggering of acute cardiovascular disease.

The increased morning frequency of cardiovascular disease onset has created concern that morning exertion promotes greater risk than evening exertion. The physiologic responses to isometric exercise (handgrip) in the morning (9 A.M.) versus the evening (6:30 P.M.) were compared in 15 subjects with mild hypertension. Isometric exercise produced similar increases at both times of the day (morning vs evening) in systolic arterial pressure (31 +/- 4 vs 35 +/- 4 mm Hg, p = NS) and heart rate (7 +/- 1 vs 8 +/- 1 beats/min, p = NS). It also produced similar increases in fibrinolytic activity (reduction in euglobulin clot lysis time) at both times of the day (-53 +/- 27 vs -53 +/- 21 minutes). However, because basal fibrinolytic activity was lower in the morning than in the evening (euglobulin clot lysis time 364 +/- 45 vs 220 +/- 33 minutes, p < 0.01), peak fibrinolytic activity after stress was also lower in the morning (312 +/- 44 vs 176 +/- 27 minutes, p < 0.01). The present study demonstrates that in subjects with hypertension, the hemostatic and hemodynamic responses to handgrip are not greater during morning versus evening exertion. This finding, plus the overall benefits of regular exercise and the low absolute risk of an event during exercise, suggests that timing of exertion is not of critical importance. However, to obtain a definitive answer to this question, further studies are needed using different potential triggers and subject populations.

Adult↗
PubMed1994

Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier.

A neglected area of cardiovascular research--study of the mechanisms of acute disease onset-is receiving increased attention. The new interest is based on the undisputed findings that onset of myocardial infarction and sudden cardiac death are more likely soon after awakening, indicating that activities of the patient frequently trigger the diseases. Triggering may occur when stressors produce hemodynamic, vasoconstrictive and prothrombotic forces--acute risk factors--that, in the presence of a vulnerable atherosclerotic plaque, cause plaque disruption and thrombosis. Triggering research may clarify mechanisms and suggest measures to sever the linkage between a potential trigger and its pathologic consequence.

Acute Disease↗
PubMed1994

Use of skin conductance changes during mental stress testing as an index of autonomic arousal in cardiovascular research.

Mental stress testing is used to study the cardiovascular changes caused by psychologic stress. To examine the effects of cardiac drugs on mental stress-induced changes, it is useful to attain a degree of arousal that can be replicated in serial studies. Skin conductance level, a cholinergically mediated index of arousal, was assessed for its stability in serial studies and under conditions of beta-blockade. In normal subjects, skin conductance increased in response to mental stress (p < 0.001) and was stable across three sessions. In patients with mild hypertension, skin conductance was elevated during mental stress during both placebo and nadolol therapy (p < 0.001). As expected, nadolol reduced baseline and stress-induced peak arterial pressure and heart rate but had no significant effect on skin conductance. Thus skin conductance level can serve as a stable and useful index of autonomic arousal in clinical trials, even in patients using beta-blocking medications.

Adult↗
PubMed1994

Similar results of percutaneous transluminal coronary angioplasty for women and men with postmyocardial infarction ischemia.

OBJECTIVES: The purpose of this study was to determine whether there are gender differences in the outcome of percutaneous transluminal coronary angioplasty performed for postmyocardial infarction ischemia. BACKGROUND: Although women have a higher mortality rate after myocardial infarction than that of men, they are less frequently referred for coronary angioplasty (and coronary artery bypass graft surgery) than are men, possibly because of expectations of a worse procedural outcome. METHODS: We analyzed the morbidity and mortality at coronary angioplasty and during a mean follow-up period of 34.4 months for women and 34.2 months for men in 505 consecutive patients (164 women and 341 men) with postmyocardial infarction ischemia between 1981 and 1989. RESULTS: Compared with men, women had similar procedural success rates (89.6% and 91.2%, respectively), need for coronary artery bypass surgery (3.7% and 2.6%) and mortality rates at coronary angioplasty (0.6% and 0.9%). During the follow-up period, there were no significant gender differences in the requirement for coronary artery bypass surgery (3.6% and 4%), repeat angioplasty (18.7% and 17.3%), reinfarction (5.8% and 6%) and death (3.6% and 3.7%) or the combined end points of all four events (26.6% and 26.6%). Women had significantly more recurrent angina than did men (54% vs. 42.5%, p < 0.01), even though the extent of coronary artery disease and frequency of incomplete revascularization were similar in men and women. CONCLUSIONS: The procedural outcome of coronary angioplasty for postmyocardial infarction ischemia is similar in women and men. Long-term follow-up is also similar except that women experience an increased incidence of recurrent angina, an outcome also reported after bypass surgery. Therefore, concerns over the safety of coronary angioplasty in women should not adversely influence decisions concerning referral of women for coronary angioplasty after myocardial infarction complicated by ischemia.

Adult↗
PubMed1994

Circadian variation and triggers of cardiovascular disease.

It has recently been shown that approximately 90% of cases of non-fatal myocardial infarction and many cases of sudden cardiac death are caused by disruption of a coronary atherosclerotic plaque, followed by occlusive thrombus formation. Secondly, the circadian pattern of myocardial infarction is well known to feature a prominent increase in the morning hours. Taken together, these factors may provide an opportunity to reduce deaths caused by cardiovascular disease. Findings indicate that, in many cases, plaque disruption and thrombus formation are triggered by the activities of the patient. It is postulated that onset occurs when a 'vulnerable' atherosclerotic plaque becomes disrupted and occlusive thrombus formation occurs. The occurrence of a myocardial infarction in the morning hours could result from the synchronization of a number of potential triggers. The importance of the recognition of the circadian variation of acute onset of myocardial infarction is that pharmacologic protection can be directed at the early waking hours. It would seem reasonable to propose that long-acting anti-ischemic agents would have an advantage over short-acting agents in providing protection against the morning occurrence of myocardial infarction. A future goal would be to design therapeutic regimens that would have the ability to sever the linkage between a potential triggering activity and the development of myocardial infarction.

Cardiovascular Diseases↗
PubMed1994

Morning increase in ambulatory ischemia in patients with stable coronary artery disease. Importance of physical activity and increased cardiac demand.

BACKGROUND: The morning increase in asymptomatic ambulatory ischemia may be due to heightened coronary tone, increased physical activity, or both. If ambulatory ischemia is primarily due to physical activity, then alterations in the schedule of physical activity should be reflected in a corresponding alteration in the occurrence of ischemia. This study was designed to examine the relation between activity patterns and the frequency of ambulatory ischemic episodes and the effect of nadolol on these relations. METHODS AND RESULTS: A double-blind, randomized, placebo-controlled, crossover trial of nadolol versus placebo was performed in 20 patients with stable coronary artery disease. At the end of each 2-week treatment phase, patients were hospitalized for 48 hours. In the hospital, there was a regular activity day (awaken and assume normal activities at 8:00 AM) and a delayed activity day (awaken at 8:00 AM, arise at 10:00 AM, and begin normal activity at noon). Ambulatory ECG monitoring was performed throughout the hospitalization. On the regular activity day, there was a morning increase in heart rate and in the number of ischemic episodes during therapy with placebo that began at 8:00 AM. In contrast, on the delayed activity day, there was a 4-hour phase shift of the increases in heart rate and the increase in ischemic episodes (ie, at noon) corresponding to the onset of physical activities. Therapy with nadolol caused a 50% reduction in the total number of ischemic episodes (129 versus 65, placebo versus nadolol; P < .02). During nadolol therapy, there was no discernible circadian peak in the number of ischemic episodes on either activity day. During placebo treatment, 87% of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. Although nadolol caused a significant reduction in the total number of episodes preceded by a heart rate increase compared with placebo (99 versus 38 episodes, P < .04), this therapy was associated with a significant increase in the number of episodes not associated with a heart rate increase (15 versus 21 episodes, P < .002). CONCLUSIONS: The morning increase in ambulatory ischemic episodes is due to physical activity patterns. The majority of ischemic episodes are preceded by a heart rate increase, and it is these episodes that are primarily responsible for the morning increase in ischemia. Therapy with nadolol caused a reduction in the total number of ischemic episodes solely by reducing those episodes preceded by a heart rate increase. In contrast, nadolol caused a significant increase in the number of ischemic episodes not associated with a heart rate increase, perhaps in part because it potentiated coronary vasoconstriction.

Aged↗
PubMed1993

Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators.

BACKGROUND: Despite anecdotal evidence suggesting that heavy physical exertion can trigger the onset of acute myocardial infarction, there have been no controlled studies of the risk of myocardial infarction during and after heavy exertion, the length of time between heavy exertion and the onset of symptoms (induction time), and whether the risk can be modified by regular physical exertion. To address these questions, we collected data from patients with confirmed myocardial infarction on their activities one hour before the onset of myocardial infarction and during control periods. METHODS: Interviews with 1228 patients conducted an average of four days after myocardial infarction provided data on their usual annual frequency of physical activity and the time, type, and intensity of physical exertion in the 26 hours before the onset of myocardial infarction. We compared the observed frequency of heavy exertion (6 or more metabolic equivalents) with the expected values using two types of self-matched analyses based on a new case-crossover study design. The low frequency of heavy exertion during the control periods was validated by data from a population-based control group of 218 subjects. RESULTS: Of the patients, 4.4 percent reported heavy exertion within one hour before the onset of myocardial infarction. The estimated relative risk of myocardial infarction in the hour after heavy physical exertion, as compared with less strenuous physical exertion or none, was 5.9 (95 percent confidence interval, 4.6 to 7.7), Among people who usually exercised less than one, one to two, three to four, or five or more times per week, the respective relative risks were 107 (95 percent confidence interval, 67 to 171), 19.4 (9.9 to 38.1), 8.6 (3.6 to 20.5), and 2.4 (1.5 to 3.7). Thus, increasing levels of habitual physical activity were associated with progressively lower relative risks. The induction time from heavy exertion to the onset of myocardial infarction was less than one hour, and symptoms usually began during the activity. CONCLUSIONS: Heavy physical exertion can trigger the onset of acute myocardial infarction, particularly in people who are habitually sedentary. Improved understanding of the mechanisms by which heavy physical exertion triggers the onset of myocardial infarction and the manner in which regular exertion protects against it would facilitate the design of new preventive approaches.

Adult↗
PubMed1993

Effects of nadolol on hemodynamic and hemostatic responses to potential mental and physical triggers of myocardial infarction in subjects with mild systemic hypertension.

Although beta-adrenergic blocking agents are known to reduce the risk of myocardial infarction, the mechanism of this protective effect is not well understood. The recent demonstration that beta blockers selectively blunt the increased morning risk of myocardial infarction suggests that these agents block the pathophysiologic consequences of stressors concentrated in the morning. We determined the effect of nadolol on the hemodynamic and hemostatic responses to mental stress and isometric exertion (handgrip), 2 potential triggers of infarction. The study was conducted in 15 subjects with mild systemic hypertension, using a placebo-controlled, double-blind, crossover design. Nadolol reduced systolic pressure and heart rate after mental stress. Poststress systolic pressure was 139 +/- 4 mm Hg during therapy with nadolol versus 161 +/- 4 mm Hg during placebo administration (p < 0.05). Heart rate increased to 61 +/- 2 during nadolol therapy versus 89 +/- 5 beats/min during placebo therapy (p < 0.05). The systolic pressure increase was similar during therapy with nadolol and placebo (29 +/- 2 vs 33 +/- 2 beats/min, p = NS); however, heart rate increase was less during nadolol therapy (4 +/- 1 vs 12 +/- 4 vs beats/min, p < 0.01). The responses to handgrip and their modification during nadolol therapy were similar to those observed after mental stress. Neither platelet aggregability nor fibrinolytic potential was altered by nadolol. Thus, nadolol modified hemodynamic indexes without altering the hemostatic indexes measured. This hemodynamic effect may contribute to the decrease in morning cardiovascular events by beta-adrenergic blockers and their well-documented cardioprotective effect.

Adult↗
PubMed1993

Comparison of long-term outcome after acute myocardial infarction in patients never graduated from high school with that in more educated patients. Multicenter Investigation of the Limitation of Infarct Size (MILIS).

The clinical course of 363 patients with acute myocardial infarction who did not complete high school education was compared with that of 453 who completed at least high school. Both the in-hospital and 4-year mortality rates were markedly greater for the less educated than for the more educated patients (13 vs 5% [p < 0.001], and 36 vs 17% [p < 0.001]). Adverse baseline characteristics were partially responsible for the increased in-hospital (p = 0.059 after adjustment) and long-term (p = 0.024 after adjustment) mortality. The less educated patients were not as likely to quit smoking after acute myocardial infarction as were the more educated ones (38 vs 49%; p < 0.05). Patients who continued smoking had a greater mortality than did those who quit (24 vs 15% [p < 0.05] for less educated, and 10 vs 4% [p < 0.05] for better educated). Therefore, greater effort should be directed to smoking cessation among the high-risk group of less educated patients. However, the smoking continuation was responsible for only a small portion of the mortality difference, suggesting unidentified causes of mortality, such as lack of compliance with therapy and possible social isolation. Despite the high-risk status of the less educated patients, cardiac catheterization tended not to be performed as frequently as in the more educated patients after discharge from the hospital (16 vs 21%; p < 0.06 at 6 months).

Aged↗
PubMed1993

Sudden cardiac death. Support for a role of triggering in causation.

Epidemiological studies have identified associations between time of day and risk of sudden cardiac death. The marked peak in the occurrence of sudden cardiac death after awakening suggests that the disease is triggered by changes that occur during this time period. Increased sympathetic stimulation is a likely cause of such triggering. In the light of the circadian variation of sudden cardiac death and the evidence linking physical activity or mental stress (both associated with activation of the sympathetic nervous system) to the disease, the role of potential triggering events should be investigated. Controlled studies are needed to determine the relative risk of activities that may trigger sudden cardiac death. Since such studies must rely on witnesses (or resuscitated patients), data quality must be closely scrutinized, and studies using case-control and case-crossover designs are needed. The epidemiological and pathophysiological data reviewed in the present article suggest a number of pathways through which activities may trigger sudden cardiac death. Different extrinsic stimuli may cause similar physiological changes that subsequently lead to acute pathological events, a decrease in the ventricular fibrillation threshold through a direct myocardial effect, or a harmful effect on the conduction system. Myocardial ischemia induced by plaque rupture and thrombosis may lead directly to myocardial electric instability. The presence of chronic structural abnormalities of the myocardial tissue or the conduction system may further lower the threshold for electric instability and ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Death, Sudden, Cardiac↗
PubMed1992

Modifiers of timing and possible triggers of acute myocardial infarction in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group.

OBJECTIVES: The aim of this study was to provide insight into the mechanism of acute myocardial infarction by determining the modifiers of timing and possible triggers of onset of infarction. BACKGROUND: A higher frequency of onset of acute myocardial infarction has been reported in the morning with a peak in the 1st 3 h after awakening. This observation suggests that the onset of infarction may be triggered by activity in the morning and at other times of the day. METHODS: The clinical history of the 3,339 patients entered into the Thrombolysis in Myocardial Infarction phase II study was analyzed to determine characteristics predicting a higher frequency of infarction between 6 AM and noon, and onset of infarction during exertion. RESULTS: A higher proportion (34.4%) of infarctions began in the morning (6 AM to noon) compared with other times of the day. Characteristics independently predicting a higher frequency between 6 AM to noon were no beta-adrenergic blocking agent use in the 24 h before infarction, no discomfort other than the index pain in the preceding 48 h, occurrence of the infarction on a weekday and no history of current smoking. In 18.7% of patients, infarction occurred during moderate or marked physical activity. Independent predictors of exertion-related infarction included male gender, no history of current smoking, white race, no use of calcium channel blocking agents or nitrates in the preceding 24 h, the absence of either chest pain at rest in the 3 weeks before infarction or any pain in the preceding 48 h, the absence of new onset angina and the presence of exertional pain in the preceding 3 weeks. Compared with patients whose infarction occurred at rest or during mild activity, those with exertion-related infarction had fewer coronary vessels with > or = 60% stenosis (p = 0.002) and were more likely to have an occluded infarct-related vessel after thrombolytic therapy (p = 0.01). CONCLUSIONS: Further study of the timing and activity at onset of infarction may provide insight into the pathophysiologic mechanisms causing acute myocardial infarction and provide clues to preventive measures.

Analysis of Variance↗
PubMed1992

Effects on platelet aggregation and fibrinolytic activity during upright posture and exercise in healthy men.

The circadian variation of acute myocardial infarction suggests that daily activities such as assuming the upright posture and performing different daily activities may trigger the onset of coronary thrombosis. Such triggering may result from unfavorable alterations in the balance between the prothrombotic and antithrombotic properties of the blood. The present study compares the effects of 2 common daily activities, assuming the upright posture and exercise, on platelet aggregation and fibrinolytic activity. In healthy male subjects, assuming the upright posture in the morning significantly increased platelet aggregation and produced only a moderate increase in fibrinolytic activity within 10 minutes. These changes were still present after 90 minutes in the upright posture. Supine posture for 45 minutes resulted in levels of fibrinolytic activity and platelet aggregation comparable to that observed before initially assuming the upright posture in the morning. Return to the supine posture for 45 minutes resulted in levels of fibrinolytic activity and platelet aggregation comparable to that observed before the initial assumption of upright posture. The changes recurred when upright posture was taken later in the day. Exercise did not increase platelet aggregation to levels beyond that produced by the upright posture, but was associated with a marked increase in fibrinolytic activity. Thus, exercise and upright posture produce distinctive alterations in the thrombogenic potential of the blood that may influence the timing of clinical vascular events.

Adult↗
PubMed1992

Increased onset of sudden cardiac death in the first three hours after awakening.

A circadian variation of sudden cardiac death has been documented, but its relation to individual time of awakening and possible triggering events has not been studied in the general population. By monitoring of mortality records in 4 cities and towns in Massachusetts, 148 potential cases of sudden cardiac death were identified. In 94 cases, the informants listed on the death certificates were contacted, the diagnosis of sudden cardiac death was established, and a telephone interview was completed within a mean of 19 days (range 8 to 28) after the death. The time of day of all 94 cases of sudden cardiac death (mean age 61 +/- 9 years, 74% men) demonstrated a circadian variation (p less than 0.05) with a peak from 9:00 A.M. to 12:00 noon. An analysis of time of death adjusted for individual wake-times of the decedents demonstrated an increased onset of sudden cardiac death during the initial 3-hour interval after awakening with a relative risk of 2.6 (95% confidence interval 1.6, 4.2) compared with other times of the day. The increased risk of sudden cardiac death soon after awakening suggests specific triggering factors or mechanisms that are particularly likely to occur during this time. The narrowing of the time interval during which the risk of sudden cardiac death is increased should facilitate the study of possible pathogenetic mechanisms and triggering factors of the disease and may aid in the design of more effective preventive strategies.

Aged↗
PubMed1992

Rapidity and duration of platelet suppression by enteric-coated aspirin in healthy young men.

The recent demonstration of aspirin's ability to prevent and reduce the severity of myocardial infarction has led to a marked increase in its use and to a need for information regarding the time-course of onset and offset of its antiplatelet effect. A study of healthy men was conducted to determine (1) the rapidity of onset of inhibition of platelet aggregation in response to adenosine diphosphate, and thromboxane A2 production after chewed enteric-coated aspirin (325 mg, n = 10); and (2) the duration of platelet inhibition after cessation of enteric-coated aspirin (325 mg) every other day for 14 days (n = 10). When chewed, enteric-coated aspirin greatly inhibited platelet aggregation response to adenosine diphosphate and thromboxane A2 production within 15 minutes. Complete recovery of platelet aggregation occurred in half of the subjects by day 3, and in 80% of the subjects by day 4; the platelet response was not affected by exercise. This study demonstrates a rapid onset of aspirin's antiplatelet effect and provides information relevant for optimal timing of initiation of aspirin for acute conditions such as myocardial infarction and unstable angina, and cessation of aspirin before surgery.

Adenosine Diphosphate↗