Cynthia Toher

Relationships Between Myocardial Bioenergetic and Left Ventricular Function in Hearts With Volume-Overload Hypertrophy

BACKGROUND Left ventricular (LV) hypertrophy secondary to volume overload can result in alterations in myocardial bioenergetics and LV dysfunction. This study examined whether bioenergetic abnormalities contribute to the pump dysfunction. METHODS AND RESULTS Severe mitral regurgitation (MR) was produced in 10 dogs by disruption of the chordal apparatus. Hemodynamics and ventricular function were examined 11.7 months later under baseline conditions and during treadmill exercise. Myocardial high-energy phosphates were measured by using magnetic resonance spectroscopy at rest, during coronary vasodilation with adenosine, and during oxidative stress induced by rapid pacing and dobutamine. Chronic MR caused a 30% increase in LV mass and a 65% increase in LV volume. In MR animals, the hemodynamic and LV function were normal at rest, but abnormalities developed during beta-blockade and exercise. Myocardial creatine phosphate-to-ATP ratios were significantly lower in each layer across the LV wall in MR hearts than normal hearts. Myocardial blood flow and coronary reserve were normal in MR hearts. Moreover, hyperperfusion did not correct the abnormal bioenergetics. Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and dobutamine infusion well. CONCLUSIONS In volume-overloaded LV hypertrophied hearts, alterations in myocardial high-energy phosphate levels do not induce abnormal mechanical performance at rest but may be related to a decreased contractile reserve during exercise.

Transcatheter closure of post-infarction ventricular septal defect with the Amplatzer Septal occluder device

There is an 80-90% mortality rate within the first 2 months of the occurrence of a post-infarction ventricular septal defect (VSD) with medical treatment alone. The muscular VSD presents a technical problem for the surgeon. Surgical treatment was unsuccessful in two patients. They were treated successfully using the Amplatzer Septal Occluder, with improvement in their condition.There is an 80-90% mortality rate within the first 2 months of the occurrence of a post-infarction ventricular septal defect (VSD) with medical treatment alone. The muscular VSD presents a technical problem for the surgeon. Surgical treatment was unsuccessful in two patients. They were treated successfully using the Amplatzer Septal Occluder, with improvement in their condition.

Timing of transesophageal echocardiography in diagnosing patent foramen ovale in patients supported with left ventricular assist device

Left ventricular assist devices unload the left ventricle and decrease left atrial pressure. This hemodynamic change may cause a right to left atrial shunt and hypoxemia in patients with patent foramen ovale. We prospectively studied the best time for performing diagnostic transesophageal echocardiography in left ventricular assist device patients. Intraoperative transesophageal echocardiography was performed in 14 patients before cardiopulmonary bypass was initiated and after left ventricular assist device was implanted. No patent foramen ovale was detected when transesophageal echocardiography was done before bypass, but a patent foramen ovale was found in 3 patients when transesophageal echocardiography was performed after left ventricular assist device was activated. Patent foramen ovale was confirmed by inspection in all three patients and surgically closed during the same procedure. There were no patent foramen ovale closure-related complications.

Echocardiographic characteristics of successful deployment of the Das AngelWings atrial septal defect closure device: initial multicenter experience in the United States.

The AngelWings device is a newer transcatheter device used for closure of secundum atrial septal defects (ASD) and patent foramen ovale (PFO), which consists of a self-centering, 2-disk system. Transesophageal echocardiography (TEE) plays a pivotal role in the deployment of the 2 disks of this device, on the appropriate sides of the atrial septum. The objective of this study is to describe the echocardiographic findings associated with successful deployment of the AngelWings device for closure of ASD and PFO. We evaluated the TEE studies of 70 patients enrolled in 4 United States centers, for closure of ASD and PFO with the AngelWings device. The TEE characteristics of successful and unsuccessful deployments were analyzed. Residual shunts across the atrial septum were assessed by TEE at the end of the procedure, 24 hours later by transthoracic echocardiography, and at 6 months by TEE. The deployment of the device was successful in 65 patients (93%). In the unsuccessful group, ASD size by TEE was larger (13.4 +/- 3.1 vs 8.9 +/- 4.7 mm, p <0.05). TEE was successful in identifying snagging of the device by intracardiac structures and prolapse of corners of the left or right atrial disk through the ASD, features that were difficult to identify by fluoroscopy. The echocardiographic characteristics outlined here are important guidelines for successful deployment of the AngelWings device.

The effect of delayed reperfusion following infarction in the rat on structural changes in viable myocardium

OBJECTIVE Evidence indicates that patency of the infarct related artery following the completion of myocardial necrosis can attenuate ventricular remodeling. Data have also demonstrated that inhibition of infarct expansion contributes to the anti-remodeling effect of delayed reperfusion. However, the influence of a patent artery on components of the remodeling process in the viable myocardium is poorly understood. METHODS Myocyte morphometrics (isolated cell technique) and collagen content (hydroxyproline analysis) were assessed 28 days following experimental myocardial infarction from rats with permanently ligated left coronary vessels (NRP; n = 10) compared with rats who underwent reperfusion 150 minutes after ligation (RP; n = 11) and a sham-operated group (n = 10). RESULTS Analysis of infarct size (planimetry) in a separate group of rats demonstrated that reperfusion at this late time point did not reduce infarct size (NRP: 33 +/- 3 vs. RP: 35 +/- 5%). Myocyte length in RP rats was less than in NRP rats in viable, non-infarcted left ventricular tissue (155 +/- 3 vs. 167 +/- 4 microns, p = 0.02), in the right ventricle (154 +/- 4 vs. 167 +/- 3 microns, p = 0.02) and in the septum (158 +/- 4 vs. 169 +/- 4 microns, p = 0.05). Reperfusion also attenuated the expected increase in cell volume compared with NRP rats (left ventricle 39.4 +/- 1.7 x 10(3) vs. 44.1 +/- 1.6 x 10(3) micron 3, p = 0.06; right ventricle 36.7 +/- 1.6 x 10(3) vs. 42.7 +/- 2.0 x 10(3) micron 3, p = 0.02; septum 41.0 +/- 1.6 x 10(3) vs. 44.2 +/- 1.8 x 10(3) micron 3, p = 0.19). Hydroxyproline content increased in the viable left ventricular tissue in both the reperfused and non-reperfused groups. CONCLUSION Reperfusion without myocardial salvage attenuates the increase in myocyte length and volume that occurs in remodeling myocardium following infarction in the rat, with no effect on the increase in collagen content. These data indicate that patency of the infarct vessel, which is known to have an inhibitory effect on infarct expansion, also has an anti-remodeling effect remote from the area perfused by this artery.

1030-8 Changes in β-Actin mRNA Expression in a Canine Model of Left Ventricular Remodeling

Increased expression of the gene coding for the cytoskeletal protein β-actin has been associated with hypertrophy in different cell systems, however its expression in cardiac tissue following myocardial injury remains largely uncharacterized. β-actin mRNA expression was examined in a canine model of left ventricular damage caused by transmyocardial, direct current shock which results in remodeling of the undamaged myocardium. Myocardial RNA was harvested from the LV of normal, unshocked dogs and from the LV distant from the scar 24 hours, 72 hours, 5 days, 10 days and 30 days after DC shock. Northern analysis indicated a 3-fold increase in β-actin mRNA expression that was sustained 5 to 30 days following DC shock. Reverse transcriptase (RT) PCR was also used to examine β-actin mRNA expression with primers derived from the human β-actin sequence. A 297 bp PCR product was generated from amplification of normal canine LV tissue. Amplification of LV tissue from DC-shocked animals resulted in a progressive change from a 297 bp to a 472 bp PCR product. The ratio of 297/472 bp product was 9/1 24 hours after shock. From 3 to 5 days after shock, RT-PCR resulted in approximately equal generation of 297 and 472 bp product. Ten to 30 days after shock the 472 bp product represented over 85% of the β-actin PCR product generated. Sequencing of these PCR products confirmed that both were closely related to β-actin. The observed change in β-actin could represent alternate splicing of a single gene or expression of two different β-actin genes. Differential expression of β-actin mRNA in canine myocardium may contribute-to the already documented growth of the viable myocardium in this model.