Heritability of treadmill running endurance in rats.

Treadmill running was evaluated as a phenotype for selective breeding for high- and low-endurance performance from a starting population of 18 male and 24 female outbred Sprague-Dawley rats. Each rat was exercised to exhaustion once per day for 5 consecutive days. The treadmill was set at a constant 15 degrees slope, and the initial velocity of 10 m/min was increased by 1 m/min every 2 min. The total distance run on the single best day out of the five trials was taken as the measure of endurance performance. The original population (males and females combined, n = 42) ran on average for 396 m. The two lowest-performing pairs and two highest-performing pairs were selectively bred through three successive generations. After three generations of selection, performance of the offspring from the high selected line averaged 659 +/- 36 m (n = 20), whereas low-performance offspring (n = 13) averaged 388 +/- 28 m. The narrow-sense heritability, calculated as the regression of individual offspring performance on midparental value for each family, was 0.39 across the three generations. This implies that 39% of the variation in running endurance performance between the low and high selected lines was determined by heritable factors.

Review: the effects of antihypertensive agents on serum lipids.

Because various antihypertensive drugs adversely affect lipid metabolism, these drugs may increase associated risks for coronary artery disease and thus offset some of the beneficial effects of blood pressure reduction. In this paper the current literature regarding the effects of antihypertensive agents on serum lipids is reviewed. Differing effects of various classes of antihypertensives are assessed to further our understanding of this very important subject.

Interaction of propranolol, verapamil, and nifedipine on the myocardial depressant effect of cocaine.

We wished to determine if drugs with negative inotropic properties would exacerbate the transient myocardial depression associated with intravenous (i.v.) cocaine administration. The influence of propranolol, nifedipine, or verapamil pretreatment on the myocardial depressant effect of cocaine was examined in 13 chronically instrumented, conscious dogs. Cocaine alone (4 mg/kg i.v.) caused significant increases in heart rate (HR), mean arterial pressure (MAP), and rate-pressure product (RPP), effects consistent with sympathetic stimulation. Regional ejection fraction (EF) (determined by two-dimensional echocardiography), however, decreased from 56 +/- 5% (mean +/- SE) at baseline to 34 +/- 6% at 1 min and to 41 +/- 5% at 2 min after cocaine administration but recovered to 49 +/- 4% at 10 min. Pretreatment with propranolol (0.5 mg/kg i.v.) blunted the rate-pressure response to cocaine by 28%. Regional EF decreased from 53 +/- 5% at baseline to 26 +/- 3% (p < 0.01 as compared with cocaine alone) at 2 min after cocaine and was still reduced at 33 +/- 3% (p < 0.001 as compared with cocaine alone) at 10 min. Pretreatment with verapamil (10 mg i.v. 10 min before cocaine) blunted the rate-pressure response very little, but regional left ventricular (LV) EF decreased less, from 58 +/- 3% to only 46 +/- 5% at 2 min, and was almost normal at 10 min (57 +/- 5%). Nifedipine [90 mg sustained-release orally (p.o.) administered 5 h earlier] also reduced the myocardial depressant effect of cocaine at 2 min [regional EF decreased from 50 +/- 2% at baseline to 38 +/- 4% (cocaine alone), 56 +/- 3 to 49 +/- 4% (nifedipine and cocaine), p < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Pseudopapillary fibroelastoma of the mitral valve.

Papillary fibroelastomas are well-recognized benign cardiac neoplasms. They are primarily asymptomatic, but occasionally are associated with neurologic and cardiac symptoms. Pseudopapillary fibroelastomas presenting with usual clinical and echocardiographic manifestations of papillary fibroelastoma but lacking characteristic histologic features have not been described previously. This article describes a 42-year-old, previously healthy female admitted with sudden hemiparesis and dysarthria. Symptoms completely resolved within 4 days. Extensive investigations revealed no etiology except for a pedunculated mitral valve mass with echocardiographic appearance suggestive of papillary fibroelastoma. Histologic staining, however, failed to reveal characteristic features of papillary fibroelastoma.

High cardiac output state in patients with multiple myeloma: case report and review of the literature.

A high cardiac output state, with or without congestive heart failure, has recently been recognized in patients with multiple myeloma. This case report deals with a 62-year-old man with multiple myeloma refractory to treatment, a high cardiac output state, and life-threatening pulmonary edema. In addition, a brief review of the literature is presented.

Two-vessel coronary artery dissection in the peripartum period. Case report and literature review.

The authors report a case of early peripartum myocardial infarction resulting from spontaneous dissection of the left anterior descending coronary artery and right coronary artery in a twenty-four-year-old woman. This is the first report of double-vessel coronary dissection involving both the left and right coronary arteries diagnosed antemortem and successfully treated.

Clinical utility of digital dobutamine stress echocardiography in the noninvasive evaluation of coronary artery disease.

Exercise electrocardiography is an established mode of evaluation for patients with suspected coronary artery disease. It also provides prognostic information and guides therapeutic management in patients with established disease. However, some patients are unable to exercise because of orthopedic problems, neurologic diseases, peripheral vascular disease, or deconditioning. In the past, these patients have been referred for angiography to help assess their disease. Recently, however, new techniques to assess myocardial perfusion and/or function, including stress echocardiography, have been used in the noninvasive assessment of coronary artery disease in this group of patients. Echocardiography has been used in combination with different drugs, including dobutamine, dipyridamole, and adenosine. Dobutamine is probably the single most studied drug for stress echocardiography. Dobutamine stress echocardiography is a safe, feasible, and valuable technique for evaluating coronary artery disease.

The effects of cocaine on cardiac electrophysiology in conscious, unsedated dogs.

This study was performed to determine the cardiac electrophysiological effects of cocaine and specifically to determine the time course of these actions. Eighteen chronically instrumented conscious dogs were tested with i.v. cocaine at doses of 1 or 4 mg/kg. The following statistically significant changes were observed 1 min following the 4 mg/kg dose of cocaine: heart rate increased from 135 +/- 8 to 186 +/- 9 beats/min, QRS duration increased from 60 +/- 5 to 74 +/- 5 ms, corrected QT interval increased from 298 +/- 7 to 339 +/- 8 ms, intraatrial conduction time increased from 27 +/- 2 to 31 +/- 3 ms, atrioventricular conduction time increased from 125 +/- 5 to 140 +/- 8 ms, and the atrial effective refractory period (ERP) increased from 101 +/- 6 to 130 +/- 9 ms. All of these parameters had returned to baseline by 10 min after cocaine administration. Corrected sinus node recovery time and the ventricular ERPs were not significantly affected by either cocaine dose. The only significant change produced by the 1 mg/kg cocaine dose was prolongation of the atrial ERP. These results suggest that cocaine causes very transient electrophysiological changes that undoubtedly represent the integrated effects of the adrenergic and local anesthetic actions of this drug.

Mechanism of cocaine-induced myocardial depression in dogs.

Cocaine causes pronounced depression of left ventricular function in conscious dogs immediately after intravenous administration. To examine this effect, 14 mongrel dogs were anesthetized with pentobarbital sodium (32 mg/kg) and instrumented with arterial and venous catheters and a Doppler blood flow transducer on the left circumflex coronary artery. Two weeks later, heart rate, blood pressure, coronary blood flow, and regional left ventricular ejection fraction (by two-dimensional echocardiography) were measured before and 1, 2, 5, and 10 minutes after cocaine (4 mg/kg i.v.), while the animals were fully conscious. Heart rate, blood pressure, and coronary blood flow were increased significantly at each time after cocaine. Regional ejection fraction, however, was depressed by 50 +/- 7%, 35 +/- 4%, and 21 +/- 4% at 1, 2, and 5 minutes after cocaine treatment, respectively. Ten minutes after cocaine treatment, regional ejection fraction had recovered to a level not significantly different from baseline. Because the observed myocardial depression after cocaine was accompanied by a large increase in the rate-pressure product, and presumably, myocardial oxygen consumption, this depression could have been secondary to increased myocardial oxygen demand not appropriately matched by an increase in coronary blood flow. To minimize the effects of cocaine on myocardial oxygen demand, a subset of six dogs received cocaine (4 mg/kg i.v.) while sedated with pentobarbital (25 mg/kg). In these dogs, cocaine did not significantly alter heart rate or blood pressure; however, regional ejection fraction was significantly depressed by 44 +/- 5% and 36 +/- 6% at 1 and 2 minutes after cocaine treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aluminum hydroxide gel on quinidine gluconate absorption.

The effect of aluminum hydroxide gel on quinidine gluconate bioavailability was studied in eight nonsmoking healthy male volunteers. Subjects were randomized to receive quinidine gluconate 648 mg with and without 30 mL of aluminum hydroxide gel. The mean area under the concentration-time curve (AUC) (23.11 +/- 5.21 mg.h/L), time to reach maximum concentration (tmax) (3.13 +/- 0.64 h), maximum serum concentration (1.44 +/- 0.41 mg/L), and elimination rate constant (0.069 +/- 0.010-h) observed during the control phase of the trial did not differ significantly (p greater than 0.05) from values obtained during the coadministration of aluminum hydroxide with quinidine gluconate (23.91 +/- 4.48 mg.h/L, 4.13 +/- 2.12 h, 1.53 +/- 0.34 mg/L, and 0.077 +/- 0.013-h, respectively). There was considerable individual variation in AUC with one subject demonstrating an increase of 35 percent and one subject demonstrating a decrease of 18 percent. There was a trend toward aluminum hydroxide delaying tmax with only one subject experiencing an earlier tmax with the coadministration of aluminum hydroxide. The results of this single-dose trial suggest that, although statistically the concurrent administration of aluminum hydroxide gel with quinidine gluconate does not significantly alter the extent of quinidine absorption, clinically significant individual variations may occasionally occur.

Sonicated echocardiographic contrast agents: reproducibility studies.

This article describes the production, analysis, and reproducibility of forming microbubbles for contrast ultrasound imaging. The sonication method used to generate microbubbles was tested by four independent observers, and a subsequent laser particle counter analysis of microbubble size and concentration determined the reproducibility of the method. The results indicated that the mean bubble size was 3.3 +/- 1.2 microns for the entire group, based on three trials of each of the four participants. The characteristics of the bubble size of the microbubbles between observers were assessed with a Poisson distribution with the reproducibility based on the sample mean for each observer's trials. Standardization and calibration of the laser particle counter was accomplished with commercially available latex spheres, sonicated albumin microspheres, and a Coulter counter analysis. Our results indicate that the sonication technique generates small microbubbles with a reproducible uniform size distribution. The method of microbubble production is reproducible and can be widely applied for use in contrast echocardiographic perfusion imaging of tissue in a variety of research and clinical studies.

Automatic detection of inter-frame motion in echocardiographic images.

Signal averaging of echocardiographic frames acquired over multiple cardiac cycles has been used to improve image quality. However, misalignment of frames from respiration, transducer or patient movement, and irregular cardiac contraction affects the quality of the resultant averaged image. A motion detection system has been developed using inter-frame subtraction and statistical pattern recognition techniques. Automatic selection of frames exhibiting significant motion in a canine cardiac model compare favorably to manual selection by cardiologists (phi = 0.94) in a test set of 103 images. This method, combined with signal averaging, has resulted in an improvement in image quality.

Acute myocardial ischemia detected in dogs by temporal variation in two-dimensional ultrasound gray level.

This study tests the hypothesis that acute myocardial ischemia induces a characteristic temporal variation in regional ultrasound amplitudes. Myocardial ischemia was created by circumflex coronary artery occlusion in seven closed-chest mongrel dogs. Ultrasound images were acquired prior to occlusion and post-occlusion on a phased-array two-dimensional system. Unprocessed ultrasound data from end-diastolic images were taken digitally for quantitative gray level analysis. Temporal variation in ultrasonic gray level of a nonischemic control region was compared to the temporal variation in gray level of the ischemic area. In the ischemic area, the average gray level for all seven dogs increased from 39.2 +/- 4.2 prior to occlusion to 42.5 +/- 4.9 at 15 minutes after occlusion, and then to 44.4 +/- 5.9, 45.3 +/- 6.2, and 47.0 +/- 6.0 at 30, 60, and 120 minutes, respectively (p less than 0.05 for control vs 15 minutes and 15 minutes vs 120 minutes). No significant changes in the average gray level of all seven dogs occurred in the nonischemic area from pre-occlusion to 2 hours post-occlusion (38.8 +/- 8.8, 38.4 +/- 8.0, 37.7 +/- 8.4, 37.8 +/- 8.5, and 38.0 +/- 8.2 for control, 15, 30, 60, and 120 minutes, respectively. These data show that regions of acute myocardial ischemia can be characterized by temporal variation in intramyocardial ultrasonic gray level, not only from the time before coronary occlusion to 15 minutes after occlusion, but also between 15 and 120 minutes in the post-occlusion period. Gray level values in nonischemic regions of the left ventricle are remarkably constant over time.