Sarah E. Katz

Differential Cardiac Effects of Growth Hormone and Insulin-like Growth Factor1 in the Rat A Combined In Vivo and In Vitro Evaluation

BACKGROUND Despite their increasing clinical use and recent evidence that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) target the heart, there has been no systematic investigation of the effects of GH and IGF-1 on the cardiovascular system. METHODS AND RESULTS Sixty normal but growing adult female rats were randomized to receive 4 weeks of treatment with GH (3.5 mg.kg-1.d-1), IGF-1 (3 mg.kg-1.d-1), a combination of the two, or placebo. Transthoracic echocardiograms were performed at baseline and at 2 weeks and 4 weeks of treatment. After the final echocardiography, rats underwent either closed-chest left ventricular (LV) catheterization or Langendorff perfusion studies. Myocyte diameter and interstitial tissue fraction were assessed by morphometric histology. Echocardiographic and ex vivo data demonstrated a LV hypertrophic response in all three groups of treated animals that was most marked in the GH group, which alone exhibited a concentric growth pattern (relative wall thickness, 0.52 versus 0.42 to 0.44 in the other groups; P < .001). At 4 weeks, cardiac index was significantly higher and total systemic vascular resistance was lower in all groups of treated animals than in control animals (both P < .001), whereas arterial blood pressure did not differ significantly. All indexes of in vivo and in vitro cardiac function were higher in GH- and IGF-1-treated rats than in control animals, whereas combination therapy yielded a blunted effect. Myocyte diameter was increased in all three treated groups without an increase in interstitial tissue. CONCLUSIONS Exogenous administration of GH and IGF-1 in the normal adult rat induces a cardiac hypertrophic response without development of significant fibrosis. Cardiac performance is increased both in vivo and in the isolated heart.

Real‐Time Intracardiac Two‐Dimensional Echocardiography: An Experimental Study of In Vivo Feasibility, Imaging Planes, and Echocardiographic Anatomy

The traditional transthoracic and transesophageal echocardiographic examination have proven to be useful imaging tools for studying cardiac morphology, pathology, and function. Recently, catheter‐based ultrasound transducers have been available for intravascular ultrasonic imaging. We supposed that echocardiographic examination performed from within the heart itself can provide useful information about cardiac structure and function, especially in settings where transthoracic or transesophageal echocardiography may be technically difficult to perform or poorly tolerated by the patient. To explore this concept, we performed intracardiac echocardiography in vivo in 22 dogs using both 5‐MHz and 20‐MHz transducers. High‐quality images were obtained in all animals. Using the higher frequency transducer, detailed images with only a limited depth of field were obtained. With the 5‐MHz transducer, a comprehensive cardiac examination was feasible from within the right atrium and inferior vena cava. We were able to visualize the great vessels, all cardiac valves, and cardiac chambers in a multitude of imaging planes. Alterations in ventricular function were instantly recognized. Color Doppler capabilities allowed visualization of flow abnormalities as well. We conclude that intracardiac echocardiography is feasible and could be potentially useful in certain clinical situations. With further research and development, this technique may have an important clinical impact in cardiac therapy and diagnosis.

Intracardiac echocardiography during simulated aortic and mitral balloon valvuloplasty: In vivo experimental studies

The feasibility of intracardiac echocardiography with a low-frequency transducer to assess catheter position and detect complications during experimental aortic and mitral balloon valvuloplasty was studied in 10 dogs. Intracardiac echocardiography was performed with a transesophageal echocardiographic probe placed in the right atrium. In all instances high-quality images of cardiac structures were obtained. The guide wire and balloon catheter were clearly seen as they crossed the valves. With inflation the balloon was seen as a hyperechoic structure. Doppler echocardiography documented aortic regurgitation after inflations. Acute pericardial effusion was instantly detected. It is concluded that intracardiac echocardiography is a potentially useful technique for cardiac imaging, assessing wire and balloon catheter position, evaluating valvular regurgitation, and instantly detecting acute pericardial effusion. Further research in humans with low-frequency, catheter-based transducers needs to be performed.

Experimental Observations on Intracavitary Imaging of Cardiac Structures with 20‐MHz Ultrasound Catheters

Recently catheter‐based ultrasound devices have become available for obtaining high‐resolution images of blood vessels. In this study we evaluated the feasibility of imaging cardiac structures using 20‐MHz ultrasound catheters. In 25 dogs, the ultrasound catheter was advanced into the right and left heart chambers percutaneously. The intravascular devices yielded images of the right atrial wall, right and left ventricular myocardia, tricuspid, pulmonic, and aortic valves, and the great vessels. Although the small depth of field inherent to the frequency range of 20 MHz limited the visualization to only portions of the cardiac chambers, the images obtained were of high resolution and allowed easy identification of the various cardiac structures. Intracardiac echocardiography was easy to perform and did not result in damage to the cardiac structures. We conclude that intracardiac echocardiography using ultrasound catheters provides a new approach to cardiac imaging and that the development of lower frequency catheters could aid in extending the potential utility of intracardiac echocardiography. (ECHOCARDIOGRAPHY, Volume 8, January 1991)

Problems and Pitfalls in the Performance and Interpretation of Color Doppler Flow Imaging

Color Doppler flow imaging has become an integral part of the echocardiographic examination. By providing real‐time, two‐dimensional spatial maps of normal and abnormal cardiac blood flows, this technique provides important information that may be used to guide patient management. The acquisition and display of color Doppler flow information may be influenced by technical factors, by the physiological condition of the patient, by abnormalities of cardiac morphology, and, on occasion, by artifact. In this article, the results of a study performed to evaluate the influence of technical factors on the color Doppler assessment of mitral regurgitation are reported. Mitral regurgitation jet area size changed significantly with variation in the control settings for color gain, color process, color map, color image resolution, and sector width. A review of those factors that influence the performance and interpretation of the color Doppler flow examination is provided and their significance discussed.

Chronic NG-Nitro-l-Arginine Methyl Ester–Induced Hypertension

Background—Chronic NG-nitro-l-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME–induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. Methods and Results—Male rats received L-NAME (50 mg · kg−1 · d−1) or no drug for 6 weeks. Rats with L-NAME–induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85±19 versus 92±16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1.00±0.03 versus 1.04±0.04 g) or hypertrophy of isolated myocytes occurred (3586±129 versus 3756±135 μm2...BACKGROUND Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.