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Biomedical subjects

G C Timmis

Publications and source records attributed to G C Timmis.

At least 37 records · Page 2Linked to original sources
PubMed1996

Prospective, randomized trial of prolonged intracoronary urokinase infusion for chronic total occlusions in native coronary arteries.

OBJECTIVES: The purpose of this study was to determine the safety and efficacy of three dosing regimens of intracoronary urokinase for facilitated angioplasty of chronic total native coronary artery occlusions. BACKGROUND: Percutaneous transluminal coronary angioplasty of chronically occluded (>3 months) native coronary arteries is associated with low initial success secondary to an inability to pass the guide wire beyond the occlusion. METHODS: Patients were enrolled if a chronic total occlusion >3 months old could not be crossed with standard angioplasty equipment. Of the 101 patients enrolled, 41 had successful guide wire passage and were excluded from urokinase treatment. The remaining 60 patients were randomized to receive one of three intracoronary dosing regimens of urokinase over 8 h (group A = 0.8 million U; group B = 1.6 million U; group C = 3.2 million U), and angioplasty was again attempted after completion of the urokinase infusion in 58 patients. RESULTS: Coronary angioplasty was successful in 32 patients (53%) (group A 52%, group B 50%, group C 59%, p = 0.86). This study had a 90% power to detect at least a 50% difference between dosing groups at alpha 0.05. Bleeding complications requiring blood transfusion did not differ significantly among the dosing groups (A 0%, B 15%, C 6%, p = 0.14), although major bleeding episodes were less common in group A (p < 0.05). There were no major procedural or in-hospital complications. Angiographic follow-up in 69% of the patients with successful angioplasty revealed target vessel patency in 91% but an angiographic restenosis rate of 59%. CONCLUSIONS: A prolonged supraselective intracoronary infusion of urokinase can be safely administered and may facilitate angioplasty of chronic total occlusions. Lower doses of urokinase are equally effective and result in fewer bleeding complications than do higher dosage regimens. Vessel patency is frequently maintained, but restenosis remains a problem.

Angioplasty, Balloon, Coronary↗
PubMed1995

Cardiac demands of heavy snow shoveling.

OBJECTIVE: To assess the physiologic responses to manual (shoveling) vs automated (electric snow thrower) snow removal in healthy, untrained men. DESIGN: Observational, controlled trial. SETTING: A community-based, acute care, teaching-research hospital. PARTICIPANTS: A volunteer sample of 10 apparently healthy untrained men (mean +/- SD age = 32.4 +/- 2.1 years) met all eligibility criteria and completed the study. INTERVENTION: Each subject cleared two 10 +/- 2-cm-high, 15-m-long tracts of heavy, wet snow in the cold (2 degrees C), using self-paced manual and automated methods, in random order, with 10- to 15-minute rest periods between each 10-minute bout of work. MAIN OUTCOME MEASURES: Heart rate, blood pressure, oxygen uptake, and perceived exertion during snow removal were compared with values obtained during maximal arm-ergometer and treadmill tests. RESULTS: Mean heart rate during shoveling was 154 and 173 beats per minute at 2 and 10 minutes, respectively, corresponding to 86% and 97% of maximal heart rate. Relative heart rate (percentage of maximal heart rate) during shoveling was inversely related to aerobic fitness (r = -0.65; P = .05). The highest heart rate and perceived exertion responses during shoveling, arm-ergometer, and treadmill testing were comparable. Systolic blood pressure during snow shoveling (198 +/- 17 mm Hg) was significantly greater (P < .003) than during arm ergometry or automated snow removal and slightly greater than during maximal treadmill testing (181 +/- 25 mm Hg). Oxygen uptake during shoveling was similar to that for arm ergometry (5.7 vs 6.3 metabolic equivalents), but lower than for treadmill testing (9.3 metabolic equivalents). Cardiorespiratory and perceived exertion responses were reduced during automated snow removal. CONCLUSION: Heavy snow shoveling elicits myocardial and aerobic demands that rival maximal treadmill and arm-ergometer testing in sedentary men. These responses may contribute to cardiovascular events reported after heavy snowfalls.

Adult↗
PubMed1994

The development of implantable cardioversion defibrillation systems: the clinical chronicle of defibrillation leads.

Clinical experience suggests that there is a significant advantage from both the standpoint of survival and thoracotomy morbidity in the use of cardioverter defibrillator implantation strategies with transvenous and subcutaneous leads. Bioengineering achievements making the latter possible remains somewhat preliminary in comparison with the highly advanced analytic technology from which the leads for bradycardia pacing have issued. Accordingly, a good deal remains to be accomplished in the technology evolution of leads for implantable cardioverter defibrillators (ICDs). While second- and third-generation leads have proved to be clinically useful, their development remains far from complete. To date most lead studies have focused on endocardial shock pathways, waveforms, and the linkage thereof affecting defibrillation thresholds. Experience suggests that asymmetric biphasic waveforms that use dual pathways (versus monophasic unidirectional shocks) yield a greater margin of safety for effective control of arrhythmias with existing ICD systems. The critical mass and region of myocardium encompassed by energy pathways, the simultaneous versus sequential pulsing of ICD antiarrhythmic discharges, as well as electrode combinations, locations, and polarity, remain under study. Although final adjudication of the superiority of endocardial systems that exclude the need for thoracotomy over those that use epicardial electrodes remains to be determined by further observational and randomized trials, it is reasonable to conclude at this juncture that ICDs with endocardial leads are feasible and facile, providing a highly promising alternative to other antiarrhythmic strategies.

Animals↗
PubMed1993

A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group.

BACKGROUND: The success of thrombolytic therapy for acute myocardial infarction is limited by bleeding complications, the impossibility of reperfusing all occluded coronary arteries, recurrent myocardial ischemia, and the relatively small number of patients who are appropriate candidates for this therapy. We hypothesized that these problems could be overcome by the use of immediate percutaneous transluminal coronary angioplasty (PTCA), without previous thrombolytic therapy. METHODS: At 12 clinical centers, 395 patients who presented within 12 hours of the onset of myocardial infarction were treated with intravenous heparin and aspirin and then randomly assigned to undergo immediate PTCA (without previous thrombolytic therapy, 195 patients) or to receive intravenous tissue plasminogen activator (t-PA, 200 patients) followed by conservative care. Radionuclide ventriculography was performed to assess ventricular function within 24 hours and at six weeks. RESULTS: Among the patients randomly assigned to PTCA, 90 percent underwent the procedure; the success rate was 97 percent, and no patient required emergency coronary-artery bypass surgery. The in-hospital mortality rates in the t-PA and PTCA groups were 6.5 and 2.6 percent, respectively (P = 0.06). In a post hoc analysis, the mortality rates in the subgroups classified as "not low risk" were 10.4 and 2.0 percent, respectively (P = 0.01). Reinfarction or death in the hospital occurred in 12.0 percent of the patients treated with t-PA and 5.1 percent of those treated with PTCA (P = 0.02). Intracranial bleeding occurred more frequently among patients who received t-PA than among those who underwent PTCA (2.0 vs. 0 percent, P = 0.05). The mean (+/- SD) ejection fractions at rest (53 +/- 13 vs. 53 +/- 13 percent) and during exercise (56 +/- 13 vs. 56 +/- 14 percent) were similar in the t-PA and PTCA groups at six weeks. By six months, reinfarction or death had occurred in 32 patients who received t-PA (16.8 percent) and 16 treated with PTCA (8.5 percent, P = 0.02). CONCLUSIONS: As compared with t-PA therapy for acute myocardial infarction, immediate PTCA reduced the combined occurrence of nonfatal reinfarction or death, was associated with a lower rate of intracranial hemorrhage, and resulted in similar left ventricular systolic function.

Adult↗
PubMed1993

Clinical and prognostic significance of serum magnesium concentration in patients with severe chronic congestive heart failure: the PROMISE Study.

OBJECTIVES: The aim of this study was to determine the prognostic significance of alterations in serum magnesium in patients with moderate to severe congestive heart failure. BACKGROUND: Reductions in serum magnesium have been postulated to play a role in promoting arrhythmias and to have an adverse impact on survival in congestive heart failure, although support for this postulate is lacking. METHODS: Serum magnesium levels were measured in 1,068 patients enrolled in a survival study of class III or IV heart failure at the time of double-blind randomization to milrinone, a phosphodiesterase inhibitor, or placebo. All patients received conventional therapy with digoxin, diuretic drugs and a converting enzyme inhibitor throughout the trial. The median follow-up period was 6.1 months (range 1 day to 20 months). RESULTS: Patients with high serum magnesium (defined as > or = 1.9 mEq/liter, n = 242) were less likely to survive than were patients with a normal magnesium level (n = 627) (p < 0.05, risk ratio = 1.41). Patients with a low magnesium level (defined as < or = 1.5 mEq/liter, n = 199) had no difference in survival compared with the group with a normal magnesium level (p = NS, risk ratio = 0.89). At baseline, the patients in the high magnesium group were older and had more severe functional and renal impairment. An analysis after adjustment for these variables demonstrated no difference in survival comparing the low, normal and high magnesium groups. Although the three groups had no difference in frequency of ventricular tachycardia, length of longest run or frequency of ventricular premature beats on baseline Holter monitoring, the group with hypomagnesemia had more frequent ventricular couplets. CONCLUSIONS: Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure. Hypomagnesemia is associated with an increase in the frequency of certain forms of ventricular ectopic activity, but this is not associated with an increase in clinical events. The higher mortality rate among the patients with hypermagnesemia is attributable to older age, more advanced heart failure and renal insufficiency.

Aged↗
PubMed1992

Randomized trial of thrombolysis versus heparin in unstable angina.

BACKGROUND: The clinical usefulness of intravenous thrombolytic therapy in unstable angina is currently unknown, despite the pathogenetic similarity of this entity to acute myocardial infarction, for which thrombolysis has enjoyed great success. To compare the clinical benefit of intravenous urokinase with that of conventional antithrombotic therapy in preventing the progression of unstable angina to new myocardial infarction, intractable angina, or death within the first 96 hours after hospitalization, 149 patients with unstable angina were randomized to one of two intravenous thrombolytic strategies. METHODS AND RESULTS: Forty-nine patients received 3 million units urokinase i.v. over 90 minutes plus intravenous heparin (group A); 47 patients received unblinded 3 million units urokinase i.v. plus 325 mg aspirin p.o. daily (group B); and 53 patients received placebo thrombolytic infusion plus full-dose heparin (group C). The primary end point of this trial was 96-hour clinical status. There were no significant differences in the baseline characteristics (age, sex, previous myocardial infarction, hypertension prevalence, diabetes, tobacco use, or previous revascularization) among the three groups. Despite an excess of minor untoward reactions for the urokinase groups (chills, 26.5% and 23.4% for groups A and B versus 0% for group C; p < 0.01), there was no significant difference with respect to major bleeds (two, none, and two for groups A, B, and C, respectively; p = NS). At 96 hours after presentation, no significant difference emerged in the incidence of new cardiac events: new myocardial infarctions developed in 10.2% of group A, 6.4% of group B, and 3.8% of group C (p = NS); intractable angina occurred in 6.1% of group A, 10.6% of group B, and 9.4% of group C (p = NS). There were no deaths. All three groups encountered a similar incidence of overall cardiac events: 16.3%, 17.0%, and 13.2% for groups A, B, and C, respectively (p = NS). Although trial enrollment was to extend to 600 patients, interim analysis led to early cessation of enrollment due to a negative trend in respect to outcome after thrombolysis. CONCLUSIONS: High-dose intravenous urokinase followed by either heparin or aspirin can be safely administered to a broad, unselected group of patients with unstable angina. However, this study suggests that no clinical advantage is conferred by urokinase, with either adjunctive antithrombotic therapy over standard heparin therapy alone, when given relatively late (mean, 8.7 hours) after admission for unstable angina. A possible detrimental effect cannot be excluded.

Angina, Unstable↗
PubMed1991

Outcome of patients with acute myocardial infarction who are ineligible for thrombolytic therapy.

OBJECTIVE: To determine what proportion of patients with acute myocardial infarction are not eligible for thrombolytic therapy and to assess their natural history. DESIGN: Retrospective chart review. SETTING: A large community-based hospital. PATIENTS: All patients with acute myocardial infarction hospitalized during a 27-month period. MEASUREMENTS: Of 1471 patients with acute myocardial infarction, 230 (16%) received thrombolytic therapy according to the protocol and an additional 97 (7%) received nonprotocol thrombolytic therapy, primary coronary balloon angioplasty, or both because of contraindications. The other 1144 patients (78%) did not receive reperfusion therapy. MAIN RESULTS: The patients who did not receive thrombolytic therapy were older, more likely to be women, and more likely to have a history of hypertension, previous myocardial infarction, or chronic angina (all comparisons, P less than 0.002). An average of 1.9 reasons for exclusion were identified per patient among the ineligible patients. Mortality was fivefold higher among ineligible patients (19%; Cl, 16% to 21%) than among protocol-treated patients (4%; Cl, 1% to 6%) (P less than 0.001). In-hospital mortality rates for excluded patients were 28% (Cl, 23% to 32%) in elderly patients (age, greater than 76 years; n = 396); 29% (Cl, 23% to 35%) in patients with stroke or bleeding risk (n = 209); 17% (Cl, 14% to 20%) in patients with delayed presentation (greater than 4 hours after the onset of chest pain; [n = 599]); 14% (Cl, 11% to 16%) in patients with an ineligible electrocardiogram (ECG) (n = 673); and 26% (Cl, 21% to 32%) in patients with a miscellaneous reason for exclusion (n = 243). Independent predictors of increased mortality were: age greater than 76 years, stroke or other bleeding risk, ineligible ECG, or the presence of two or more exclusion criteria. CONCLUSIONS: Thrombolytic therapy is currently used in the United States for only a minority of patients with acute myocardial infarction: those who have low-risk prognostic characteristics.

Age Factors↗
PubMed1991

Effect of peripheral cardiopulmonary bypass on left ventricular size, afterload and myocardial function during elective supported coronary angioplasty.

Although cardiopulmonary bypass support has been increasingly used for high risk coronary angioplasty, few data exist regarding its effects on left ventricular function. Accordingly, in 20 patients changes in left ventricular size, afterload and myocardial function were assessed by continuous hemodynamic monitoring and simultaneous two-dimensional echocardiography during cardiopulmonary bypass-supported high risk angioplasty. The cross-sectional left ventricular area during bypass support remained unchanged during diastole, whereas during systole it decreased (from 29.6 +/- 11.4 to 27.6 +/- 10.4 cm2, p less than 0.05). Global left ventricular function expressed as fractional area change remained unchanged from baseline to bypass support but decreased during balloon inflation (from 0.27 +/- 0.11 to 0.17 +/- 0.09, p less than 0.001). The end-systolic meridional wall stress decreased during bypass support (from 141 +/- 75 to 110 +/- 58 x 10(3) dynes/cm2, p less than 0.02). Regional myocardial function was assessed by a wall motion score (0 = normal, 1 = hypokinesia, 2 = akinesia and 3 = dyskinesia). Regions supplied by a stenotic (greater than or equal to 50% diameter) vessel deteriorated during bypass support (score from 0.9 +/- 0.8 to 1.06 +/- 0.8, p less than 0.01), whereas regions supplied by a nonstenotic vessel did not. Regions supplied by the target vessel deteriorated further during balloon inflation (score from 0.7 +/- 0.6 to 1.7 +/- 0.75, p less than 0.001). Thus, although left ventricular size and global function remain unchanged and afterload decreases during bypass support, myocardial dysfunction in regions supplied by a stenotic vessel may occur. Furthermore, regional and global left ventricular dysfunction still occur with angioplasty balloon inflation during cardiopulmonary bypass support.

Aged↗
PubMed1991

Effects of 7 successive days of unaccustomed prolonged exercise on aerobic performance and tissue damage in fitness joggers.

The effects of 7 successive days of prolonged jogging on aerobic performance and biochemical markers of muscle and red blood cell damage were examined in 10 moderately fit men, ages 27 +/- 2 yr (mean +/- SE). The subjects jogged for 2 h per day at 78 +/- 4% of maximal heart rates and covered a total of 129 +/- 2 km, nearly eight times their regular weekly training distance. At baseline, maximal oxygen uptake (VO2max) during treadmill tests averaged 3.45 +/- 0.24 L/min, or 44.7 +/- 1.4 ml/kg/min. On follow-up tests 2d after the week of increased training, VO2max (3.56 +/- 0.17 L/min) and treadmill performance were not significantly improved. Body weight declined from 79.5 +/- 4.6 kg to 77.8 +/- 4.4 kg (p less than 0.05) because of reduced body fatness (16.8 +/- 2.3% to 13.6 +/- 1.7%, p less than 0.05). Weight-adjusted VO2max increased to 46.4 +/- 2.0 ml/kg/min (p less than 0.05). However, heart rate and systolic blood pressure were not significantly changed at rest, or during submaximal and maximal treadmill exercise. Mean hemoglobin concentration at treadmill testing declined from 14.9 +/- 0.3 g/dl to 13.3 +/- 0.3 g/dl (p less than 0.05). Leg muscle soreness, especially in the thigh region, persisted in all subjects after 3 d. Soreness was accompanied by chronic elevations (p less than 0.05) in serum levels of myoglobin, creatine kinase (CK), lactic dehydrogenase (LD), aminoaspartate, and the isoenzymes CK-MB and LD1,2. Serum haptoglobin levels after jogging fell from 86 +/- 9 mg/dl to 60 +/- 8 mg/dl (p less than 0.05), suggestive of footstrike hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗