Factors regulating condylar cartilage growth under repeated load application.

Mechanical loading can influence the biological behavior of the bone-associated cells leading to adaptive changes in skeletal mass and architecture. SOX9 and PTHrP genes are known to regulate chondrocyte differentiation and delay maturation, ultimately control the endochondral bone formation. To investigate the effects of repeated mechanical loading on bone, 280 Sprague-Dawley rats were used in this experiment. The animals were randomly allocated into experimental and control groups. Repeated mechanical loading was applied through a bite-jumping device in the experimental group. The experimental animals were sacrificed on 10 different time points together with the matched control. Total RNA was extracted from the mandibular condylar cartilage for PTHrP and SOX9 genes quantification using real-time RTPCR. Results showed that PTHrP expression was increased and reached a peak level on the seventh day after mechanical loading was given. Repeated mechanical loading triggered a significant increase of PTHrP expression leading to another peak increment. The expression of SOX9 was highly correlated with the PTHrP expression, and its pattern of expression was similar to that of PTHrP after repeated mechanical loading. In conclusions, repeated mechanical loading on the condyle triggers the expression of PTHrP and SOX9, which in turn promotes condylar cartilage growth.

Effects of left ventricular pressure on sonicated albumin microbubbles: evaluation using an isolated rabbit heart model.

OBJECTIVES: We used an isolated, crystalloid-perfused rabbit heart model to test the hypothesis that the phasic changes in left ventricular contrast are due to bubble compression and decompression during systole and diastole, respectively. BACKGROUND: Contrast enhancement of the left ventricular cavity has been shown to decrease during ventricular systole. This phenomenon has been attributed to pressure-induced microbubble destruction. Such destruction, if confirmed, would severely confound the quantitative interpretation of contrast echocardiographic data. METHODS: A fixed volume of contrast solution (5% human albumin and Albunex, approximately 400:1 ratio) was introduced into a latex balloon placed within the left ventricular cavity of an isolated paced rabbit heart preparation (n = 12). Instantaneous left ventricular pressure was measured using a high fidelity microtip catheter and digitized on-line. The beating heart was placed in a water tank, and ultrasound images were obtained using a 7.5-MHz transducer and were recorded and digitized off-line at 12 frames/s. Simultaneously, the pacing signal was used for gated on-line acquisition of end-diastolic frames. A simple theoretic model based on surface tension physical principles was used to predict changes in bubble size and, consequently, the reflection intensity in response to the measured changes in left ventricular pressure. RESULTS: We found that under peak left ventricular systolic pressures ranging from 89 to 155 mm Hg, 1) end-diastolic videointensity decreased by 8 +/- 6% (mean +/- SD) over 25 consecutive heart beats; and 2) intracyclic variations in measured videointensity were in close agreement with the theoretic calculations: 80.1 +/- 2.9% versus 80.2 +/- 4.6% of diastolic videointensity at systole. CONCLUSIONS: The major cause of systolic decrease in contrast enhancement is periodic bubble compression (as opposed to bubble destruction) induced by high systolic pressures. The minor progressive decrease in end-diastolic videointensity reflects the degree of instability of Albunex microbubbles under left ventricular pressures. However, the clinical impact of these destructive effects is likely to be only minor because of the rapid transit of microbubbles through the left heart chambers and myocardial microcirculation.

Pericardial cyst causing right ventricular outflow tract obstruction.

Pleuropericardial cysts are rare. Rarer still are cardiopulmonary complications caused by their presence. We report the case of a pericardial cyst producing high-grade right ventricular outflow tract obstruction and its subsequent management. The clinical importance of transesophageal echocardiography is highlighted.

Contrast echocardiographic quantification of regional myocardial perfusion: validation with an isolated rabbit heart model.

Quantification of regional myocardial tissue blood flow (RMBF) based on contrast echocardiography has yet to be achieved. This study validated our recently proposed algorithm for quantification of RMBF with colored microspheres. Experiments were carried out in an isolated rabbit heart preparation (n = 11). Aortic root injections of perfluoropropane-filled albumin microsphere solution (FS069) and colored microspheres were performed at five levels of coronary flow achieved by altering perfusion pressure. During each injection of contrast material, consecutive end-diastolic images of the heart and an extracardiac reference chamber were acquired with a 7.5 MHz transducer and digitized. Time-intensity curves from the reference chamber and myocardial regions of interest, corresponding to the anatomic segments used for colored microsphere analysis, were analyzed for RMBF. Blood flow was calculated as the intravascular volume fraction (ratio of areas under myocardial and reference curves) divided by mean transit time (deconvolution of impulse response) and compared with those obtained with colored microspheres. Injections of FS069 resulted in highly reproducible enhancement of myocardial contrast. Analysis of time-intensity curves provided consistent measurements of RMBF (r = 0.91), which correlated highly with microsphere data (r = 0.84). The use of this new algorithm allows accurate quantification of RMBF in the isolated heart model. Further validation of this approach in an animal model with peripheral intravenous injections of contrast material will allow noninvasive clinical measurements of RMBF.

Echocardiographic contrast agents and left ventricular contractility: evaluation using an isolated rabbit heart model.

The effects of Albunex (Molecular Biosystems, Inc., San Diego, Calif.) and a second generation contrast agent, FS069, on left ventricular (LV) contractility were evaluated using an isolated rabbit heart model under constant loading conditions and heart rate. Contrast injections (2 ml total volume) were performed in two separate protocols (N1 = 6, N2 = 6). In protocol 1, various doses of Albunex (0.1 to 2.0 ml in saline solution) were used, and paired control injections of a matched dose of 5% solution of human albumin in saline solution were administered. In protocol 2, LV contractility was assessed during injections of the following solutions: (1) 1:250 suspension of FS069 in saline solution, which caused optimal myocardial contrast enhancement; (2) a 1:25 suspension of FS069; (3) a 1:25 suspension of FS069 prefiltered using an 8 microns pore filter; and (4) 2 ml saline solution as a control. Instantaneous LV pressure was analyzed for variations in peak systolic pressure (peak P) and maximum pressure derivative (peak P'), both indices of LV contractility under conditions of fixed heart rate and chamber volume. Albumin alone caused a transient, dose-dependent depression of LV contractility, reflected by decreases in both peak P and peak P' values. These decreases presumably were caused by the decreasing availability of ionized calcium as a result of calcium binding. No further decrease in contractility was noted when Albunex microspheres were present in the solution. Saline injections caused a transient minor increase in LV contractility, reflected by increases of 4.5% +/- 1.1% and 10.6% +/- 3.8% in peak P and peak P' values, respectively. These levels returned to baseline levels within 2 minutes. A similar response was observed when a 1:250 suspension of FS069 was used. The 1:25 suspension of FS069 caused a bimodal response, with initial rises in peak P and peak P' levels (5.2% +/- 3.6% and 12.8% +/- 6.5%, respectively), followed by minor reductions in contractility (2.0% +/- 2.4% and 1.7% +/- 2.1%, respectively). The latter decrease in contractility caused by the 1:25 suspension of FS069 was eliminated by filtering. The isolated rabbit heart model is a highly sensitive tool that allows accurate and direct assessment of possible adverse effects of intravascular contrast agents on LV contractility. Using this model, we showed that neither Albunex microspheres nor FS069 microspheres impaired myocardial contractility.