Gary V. Martin

The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial.

Three hundred sixty-eight patients were randomly assigned to receive intravenous streptokinase (IVSK) (n = 191) or standard therapy (n = 177) to determine the efficacy of IVSK in the treatment of acute myocardial infarction. The mean time to treatment was 3.5 hr. At 14 days there were 12 deaths in the treatment group (6.3%) and 17 deaths in the control group (9.6%) (p = .23). Early mortality was related to infarct location. Fourteen day mortality for anterior infarctions was 10.4% for treatment with IVSK and 22.4% for control patients (p = .06) and was similar for IVSK-treated patients with inferior infarctions, 4.0% vs 1.8% (p = .32). For those randomized under 3 hr, 14 day mortality tends to be lower in treated patients, 5.2% vs 11.5% (p = .11). There was significant improvement in long-term survival for patients with anterior infarction; 2 year survival was 81% for IVSK-treated patients and 65% for control patients (p = .05). There was no improvement in survival for patients with inferior myocardial infarction (p = .27). We conclude that patients with anterior myocardial infarction have improved survival when treated within the first 6 hr of symptoms. Patients with inferior infarction do not appear to have improved survival with thrombolytic therapy. Some of this improvement in survival in patients with anterior infarction may be due to a higher frequency of revascularization procedures in the treatment group.

Intravenous streptokinase for acute myocardial infarction. Effects on global and regional systolic function.

The Western Washington Intravenous Streptokinase Trial randomized 368 patients with acute myocardial infarction to receive either intravenous streptokinase or standard therapy. The ventriculograms and coronary angiograms obtained in 170 patients 10.4 +/- 7.4 days after infarction were analyzed to evaluate the effects of thrombolytic therapy on global and regional systolic function. Streptokinase treatment resulted in a higher patency rate of the infarct-related artery (68.5%) than did standard therapy (44.8%) (p = 0.003). Ejection fraction was higher in streptokinase-treated patients (54% vs. 51%, p = 0.056), and the difference was most marked in patients with anterior myocardial infarction (53% vs. 44%, p = 0.03). Regional wall motion was measured by the centerline method and expressed in mean +/- SD motion in 52 normal subjects. There was a trend toward better function of the infarct zone in streptokinase-treated patients (SD, -2.48 vs. -2.70, p = 0.24). Additionally, streptokinase-treated patients had significantly better wall motion of noninfarct areas (SD, 0.36 vs. -0.08, p = 0.02). Treatment effects on function of noninfarct regions were most apparent in the subset of patients with multivessel disease. Thus, intravenous streptokinase preserves left ventricular function in patients with acute myocardial infarction. This benefit includes favorable effects on the function of regions remote from the site of infarction.

Frequency of serum low-density lipoprotein cholesterol measurement and frequency of results ≤100 mg/dl among patients who had coronary events (Northwest VA Network Study) ∗

This population-based, cross-sectional analysis targeted all veterans with coronary heart disease (CHD) who were active patients in primary care or cardiology clinics in the Veterans Health Administration Northwest Network from July 1998 to June 1999. We report guideline compliance rates, including whether low-density lipoprotein (LDL) was measured, and if measured, whether the LDL was < or=100 mg/dl. In addition, we utilized multivariate logistic regression to determine patient characteristics associated with LDL measurements and levels. Of 13,891 active patients with CHD, 5,552 (40.0%) did not have a current LDL measurement. Of those with LDL measurements, 39.1% were at the LDL goal of < or =100 mg/dl, whereas 26.5% had LDL > or =130 mg/dl. Male gender, younger age, history of angioplasty or coronary artery bypass grafting, current hypertension, diabetes mellitus, and angina pectoris were associated with increased likelihood of LDL measurement. Older age and current diabetes and angina were associated with increased likelihood of LDL being < or =100 mg/dl, if measured. Although these rates of guideline adherence in the CHD population compare well to previously published results, they continue to be unacceptably low for optimal clinical outcomes. Attention to both LDL measurement and treatment (if elevated) is warranted.

Relation of global and regional left ventricular function to tomographic thallium-201 myocardial perfusion in patients with prior myocardial infarction☆

To determine the relation between regional myocardial perfusion and regional wall motion in humans, tomographic thallium-201 imaging and two-dimensional echocardiography at rest were performed on the same day in 83 patients 4 to 12 weeks after myocardial infarction. Myocardial perfusion and wall motion were assessed independently in five left ventricular regions (total 415 regions). Regional myocardial perfusion was quantitated as a percent of the region infarcted (range 0 to 100%) using a previously validated method. Wall motion was graded on a four point scale as 1 = normal (n = 266 regions), 2 = hypokinesia (n = 64), 3 = akinesia (n = 70), 4 = dyskinesia (n = 13) or not evaluable (n = 2). Regional wall motion correlated directly with the severity of the perfusion deficit (r = 0.68, p less than 0.0001). Among normally contracting regions, the mean perfusion defect score was only 2 +/- 4. Increasingly severe wall motion abnormalities were associated with larger perfusion defect scores (hypokinesia = 6 +/- 5, akinesia = 11 +/- 7 and dyskinesia = 18 +/- 5, all p less than 0.01 versus normal. Among regions with normal wall motion, only 3% had a perfusion defect score greater than or equal to 10. Conversely, among 68 regions with a large (greater than or equal to 10) perfusion defect, only 13% had normal motion whereas 87% had abnormal wall motion. The relation between perfusion and wall motion noted for the entire cohort was also present in subgroups of patients with anterior or inferior infarction. In patients with prior myocardial infarction, the severity of the tomographic thallium perfusion defect correlates directly with echocardiographically defined wall motion abnormalities, both globally and regionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantifying Hypoxia with Radiolabeled Fluoromisonidazole: Pre-Clinical and Clinical Studies

The efforts to image hypoxia in oncology were stimulated by several questions about tumor biology and its role in response to treatment. What biochemical or physiological properties of tumors influence outcome of therapy? What drug or molecule is a natural substrate, precursor, or marker for the property of interest? Which characteristics of tumors are quantitatively, if not qualitatively different from normal tissues? Tumor hypoxia emerged as a feature that limits response to both radiation and chemotherapy and distinguishes tumors from nondiseased normal tissues, which are adequately oxygenated. It also appeared amenable to quantitation with PET imaging, provided one could develop an appropriate radiopharmaceutical that gave a positive image of oxygen-deprived tissue. A PET image of the metabolic rate of oxygen using [15O]O2 would produce a less desirable negative image for tissue with reduced oxygenation. Consideration of nonmalignant disease also identified two additional conditions where noninvasive quantification of oxygenation might be useful: myocardial infarct and cerebral ischemia.

Transthoracic Contrast Echocardiographic Detection of Ascending Aortic Dissection

BACKGROUND Ascending aortic dissection is highly lethal if left untreated. Therefore rapid accurate diagnosis is necessary. Diagnosis can be made with imaging modalities that use contrast agents to delineate anatomy reliably. Transthoracic echocardiography has not routinely been diagnostically useful because of the inability in clearly visualizing the ascending aorta. METHOD AND RESULTS We describe a case in which transthoracic echocardiography with an echocardiographic contrast agent provided diagnostic information regarding an acute ascending aortic dissection, delineating both the true and false lumens. CONCLUSIONS Transthoracic echocardiography combined with an echocardiographic contrast agent can be useful in detecting an ascending aortic dissection.

Effects of α2-adrenergic stimulation with UK 14,304-18 on the heart and peripheral circulation of intact dogs

Summary: To determine the extent of α2-adrenoreceptor control of cardiovascular function, we studied the hemodynamic effects of the relatively selective α2-adrenergic agonist UK 14,304-18 on the heart and peripheral circulation of intact dogs. Administration of increasing intravenous doses of UK 14,304-18 to conscious dogs given atropine to maintain heart rate (HR) resulted in a reproducible increase in mean aortic (AO) pressure (77.6 ± 5.0 to 136.4 ± 6.5 mm Hg, p < 0.05) and reductions in stroke volume (31.7 ± 2.9 to 17.9 ± 1.9 ml/kg/min, p < 0.05) and left ventricular (LV) dP/dt (2,120 ± 280.0 to 1,463 ± 196.1 mm Hg/s, p < 0.05). In ganglion-blocked dogs UK 14,304-18 did not alter the slope of the LV endsystolic pressure–volume relationship when compared with angiotensin and nitroprusside (79.9 ± 11.1 control vs. 73.3 ± 8.7 mm Hg/ml/kg UK 14,304-18, p > 0.05), nor did it change the volume intercept (−0.46 ± 0.12 control vs. −0.53 ± 0.16 ml/kg UK 14,304-18, p > 0.05) indicating no direct effect on LV contractile function. Changes in indices of diastolic function, including the time constant of isovolumic relaxation, time to peak filling, and chamber volume elasticity were similar to those of equipressor doses of angiotensin, indicating no direct effect on LV diastolic function. Effects on the peripheral circulation were studied in dogs undergoing transient acetylcholine-induced circulatory arrest. UK 14,304-18 increased mean circulatory filling pressure (7.9 ± 0.3 to 10.3 ± 0.2 mm Hg, p < 0.05) and the pressure gradient for venous return (7.6 ± 0.4 to 9.0 ± 0.3 mm Hg, p < 0.05). Central blood volume increased with UK 14,304-18 (15.6 ± 1.1 to 18.7 ± 1.5 ml/kg, p < 0.05), but this increase was not sufficient to maintain cardiac output (CO) during the UK 14,304-18 infusion, which decreased from 157.4 ± 11.1 to 131.5 ± 8.9 ml/kg/min (p < 0.01) in the presence of increased LV afterload. The time constant of relaxation of the arterial system increased and the arterial compliance decreased with increasing mean arterial pressure. Thus, this relatively selective α2 agonist does not directly alter cardiac function but increases tone in arterial resistance vessels and in systemic veins. The fall in CO appears to be caused by a mismatch between preload and afterload, which is the net result of quantitatively different effects on systemic veins and arteries.

Are Flow Transport Capacities and Metabolic Requirements Matched Regionally in the Myocardium

Data were acquired on the uptake of metabolic substrates and on well-retained ions in small regions of the myocardium, 1 to 2 min after injection into the left atrium, and compared with estimates of local myocardial blood flows in each of the 250 to 500 regions, per heart. The data showed approximately linear relationships between the deposition of these solutes and the local flows. Models for blood-tissue exchange kinetics based on an assumption of the constancy of permeability-surface area products for capillary and cellular uptake in all regions being the same were not compatible with the data. Using axially distributed multiregional models appropriate to the solutes, the data could be fitted only when the permeability-surface area products were proportional to the local flow in each region. Within myocardial pieces of 0.1 to 0.2 G, the range of flows was about six-fold; if within the pieces having the lowest flows the regional metabolism was at the average rate for the whole heart, tissue viability could not be supported by flows available. These regions must therefore have less than average metabolic requirements. Likewise high flow regions would be extravagantly perfused if their metabolic rates were at the average rate. We conclude that although the link between transport capacities and flow is well established, that between local metabolism and flows is not proven, but it is highly likely that local flows transport capacities and metabolic requirements are well matched.

Imaging Hypoxic Myocardium

An appropriate oxygen tension is a basic condition for normal cardiac function. Most of the energy needs of the myocyte are met by oxidative processes, and oxygen deficiency results in the metabolic and functional abnormalities associated with ischemic heart disease. Despite the central importance of tissue pO2 in normal and pathophysiological cardiac function, little is known about intracellular pO2 in the human heart. There is also uncertainty about what level of pO2 constitutes tissue hypoxia. Contractile abnormalities occur when coronary sinus pO2 is reduced to 10–15 mmHg, but in vitro normal mitochondrial function is supported at much lower pO2 [1].