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L Aklog

Publications and source records attributed to L Aklog.

26 records · Page 2Linked to original sources

Right latissimus dorsi cardiomyoplasty improves left ventricular function by increasing peak systolic elastance (Emax).

BACKGROUND: Dynamic cardiomyoplasty remains a promising but poorly understood surgical modality for selected patients with dilated cardiomyopathy. Despite encouraging clinical results, objective evidence of enhanced ventricular function using traditional indexes (cardiac output, ejection fraction, and dP/dt) has been difficult to document after cardiomyoplasty. Several investigators have suggested that cardiomyoplasty acts partly by unloading the left ventricle. These indexes all depend somewhat on loading conditions, however, and might not detect such an interaction. The time-varying elastance model provides an index of contractility, Emax, that is relatively insensitive to changes in loading conditions. We applied this model to study the effect of right latissimus dorsi cardiomyoplasty on left ventricular function in an acute canine model. METHODS AND RESULTS: Five dogs underwent acute cardiomyoplasty using untrained right latissimus dorsi muscle. Instrumentation included Millar pressure transducers in the left ventricle and aortic root, an electromagnetic flow probe around the ascending aorta, and a volume conductance catheter in the left ventricle. A cuffed nerve electrode around the thoracodorsal nerve and a right ventricular sensing lead were connected to a Medtronic Cardiomyostimulator (5 V, 30 Hz, 1:1 synchronization). Transient caval occlusions were performed with the stimulator both off and on to calculate Emax and the slope of the end-systolic pressure-volume relationship (Ees). Turning the stimulator on significantly increased peak systolic elastance (Emax) and end-systolic elastance (Ees) in all five dogs by an average of 56% and 78%, respectively (P < .05). End-diastolic volume and end-systolic volume decreased by 18% and 28%, respectively (P < .05). All other measured hemodynamic parameters, including peak left ventricular pressure, mean arterial pressure, cardiac output, stroke volume, stroke work, ejection fraction, preload-recruitable stroke work, and dP/dt, did not change significantly. CONCLUSIONS: These results show that, in this acute canine model, right latissimus dorsi cardiomyoplasty significantly improves left ventricular function while decreasing left ventricular volumes. The results are consistent with the theory that cardiomyoplasty increases contractility while unloading the ventricle by decreasing end-diastolic volume. This increase in Emax despite inconsistent changes in other indexes underlies the importance of using load-insensitive indexes of ventricular function when studying cardiomyoplasty.

Animals↗

Rapid noninvasive diagnosis and surgical repair of acute ascending aortic dissection. Improved survival with less angiography.

Angiography has been considered the gold standard for the diagnosis of acute dissection of the ascending aorta, but it may increase mortality by imposing an unnecessary delay before surgical repair. In addition, coronary angiography has often been considered essential as well. From 1988 to 1993, 37 patients (median age 61 years, 30 men and 7 women) had acute dissection of the ascending aorta. All of the initial 15 patients (group I) had angiography, even through the diagnosis of aortic dissection had already been made noninvasively in 14; six (40%) of 15 died, three of aortic rupture and none of complications of coronary artery disease. Among the next 22 patients (group II), 21 had a noninvasive diagnosis of acute dissection of the ascending aorta (eight by echocardiography; 13 by computed tomography), and 19 (86%) were operated on without angiography; two died (9%, p = 0.03 versus group I) and neither death was due to aortic rupture or coronary artery disease. Overall, either root or selective coronary angiography was attempted in 18 of 37 patients, but it documented coronary artery disease in only two patients (11%). Coronary artery disease was found in four other patents at autopsy; three of them, including two that died of aortic rupture, had angiography that failed to reveal the coronary artery disease. Noninvasive diagnosis of acute dissection of the ascending aorta is reliable and avoids the risks and delays inherent in invasive angiography. Rapid noninvasive diagnosis of aortic dissection and avoidance of routine angiography appear to improve survival by expediting surgical intervention and thus decreasing the risk of aortic rupture.

Acute Disease↗

Prevention of complement-induced pulmonary hypertension and improvement of right ventricular function by selective thromboxane receptor antagonism.

The effect of complement activation on the pulmonary vascular system and on right ventricular function was studied in sheep (n = 12) by injection of cobra venom factor. Animals were instrumented for measurement of pulmonary flow, mean pulmonary artery pressure, right ventricular stroke work, arterial blood gases, and systemic vascular resistance. Blood was sampled from the left atrium and pulmonary artery to measure thromboxane B2, the metabolite of thromboxane A2, by radioimmunoassay. After baseline measurements, animals were randomly assigned to receive a selective thromboxane receptor antagonist SQ30741 as a 10 mg/kg bolus with an infusion of 10 mg/kg per hour or else to receive vehicle. Cobra venom factor was then injected (30 U/kg) in all animals, and data were recorded at 15, 30, 60, 90, and 120 minutes. In control animals there was a 2.4-fold increase in mean pulmonary artery pressure and a 76% increase in right ventricular stroke work at 15 minutes from baseline (p < 0.05); these values remained elevated for 30 minutes and returned to baseline by 1 hour with no change in systemic vascular resistance. Arterial oxygenation decreased by 124% at 15 minutes and remained depressed through the experiment, but in treated animals oxygen tension remained unchanged from baseline. Thromboxane B2 increased 95% from baseline in the control group and 1.5 fold in treated animals and followed a similar time course as the functional measurements (p < 0.05). A pulmonary vascular thromboxane B2 gradient of approximately 1000 pg/ml was measured at 15 and 30 minutes in both control and treated groups. (p < 0.05) We conclude that after complement activation in this model pulmonary hypertension and decreased oxygen tension are mediated by thromboxane release from the pulmonary vascular bed. This increased afterload causes a stress on the right ventricle as demonstrated by the increased right ventricular stroke work. Selective thromboxane receptor antagonism may be a beneficial therapy for pulmonary hypertension in patients after cardiopulmonary bypass.

Animals↗

Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.

Profilin is a conserved actin-monomer-binding protein which is found in all eukaryotes, including yeast. Although amino acid sequence analysis and RNase protection analysis suggest a single profilin isoform in mammalian cells, Southern blot analysis of human and somatic cell hybrid DNA indicates several loci in the human genome which hybridize with the profilin cDNA. We therefore isolated human genomic clones to analyze these genetic loci in detail. Only one of the cloned loci has typical features of a functional gene, including upstream transcriptional elements and typical exon-intron structure. Four other isolated loci are all diverged, intronless pseudogenes and are likely to be nonfunctional. The functional gene was localized to human chromosome band 17p13 by analysis of somatic cell hybrids and by in situ chromosomal localization. The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region. RFLP analysis of a patient with MDS, and analysis of somatic cell hybrids containing partially deleted chromosomes 17 from patients with MDS, using the profilin gene probe, indicate that profilin is localized to chromosome subband 17p13.3. These results also indicate that profilin is the first identified cloned gene which is part of the genetic material deleted in some patients with MDS but that other patients have smaller deletions not affecting the profilin locus. Thus, single allelic deletion of the profilin locus may contribute to the clinical phenotype of the MDS in some patients but does not play a major role in the essential phenotype.

Amino Acid Sequence↗

Minimally invasive direct access heart valve surgery.

We review our experience with minimally invasive direct access (MIDA) heart valve surgery in 518 patients. Two hundred fifty-two patients underwent MIDA aortic valve replacement (AVR) or repair and 266 underwent MIDA mitral valve repair or replacement. Among the 250 AVRs, 157 (63%) were men, aged 63.2 +/- 14.6 years, NYHA functional Class 2.4 +/- 0.8. The surgical approach was right parasternal in 36 (14%) or upper hemisternotomy in 216 (86%). There were four (2%) operative deaths. Perioperative complications included 14 (5.6%) reexplorations for bleeding, 7 (3%) chest wound infections, 5 (2%) strokes, and 1 (0.4%) external iliac vein injury. Follow-up was complete in 193 (77%) patients, with a mean follow-up of 12 +/- 8 months. Late complications included 2 (0.8%) nonfatal myocardial infarctions, 4 (2%) reoperations for, respectively, 2 pericardial complications, 1 paravalvar leak, and 1 infected valve. There were five (2%) late deaths from congestive heart failure, pneumonia, hemorrhage, aneurysm, and cancer. Mean follow-up NYHA Class was 1.4 +/- 0.6. For the 266 mitral patients, 145 (54.5%) were men, age 58.7 +/- 13.6 years, functional Class 2.3 +/- 0.5. The surgical approach was right parasternal in 195 (73%), lower hemisternotomy in 53 (20%), right submammary thoracotomy in 9 (3.4%), or full sternotomy through a small skin incision in 9 (3.4%). There were 2 (0.8%) operative deaths. Perioperative complications included 4 (1.5%) reoperations for bleeding, 4 (1.5%) strokes, and 5 (2%) wound infections, and 3 (1%) ascending aortic complications. Follow-up was complete in 202 (76%) patients with a mean follow-up of 9.5 +/- 6.4 months. Late complications included one (0.4%) nonfatal myocardial infarction and three (1%) reoperations all converting repairs to replacements. There were three (1%) late deaths from suicide, pneumonia, and sudden death, respectively. Mean follow-up NYHA functional Class was 1.3 +/- 0.5. We conclude that MIDA heart valve surgery is safe and effective for the majority of patients requiring isolated elective aortic or mitral valve surgery.

Adolescent↗

Mitral valve repair in redo cardiac surgery.

An increasing number of patients are being referred for mitral valve repair in the redo cardiac surgery setting. The most common clinical scenarios involve prior coronary bypass surgery or aortic valve replacement, each presenting special challenges in terms of gaining valve exposure to enable repair while limiting dissection as much as possible. A right anterior thoracotomy approach is preferred in most patients, coupled with hypothermic fibrillatory arrest. A repeat sternotomy may be favored in select circumstances such as when there is a need for bypass grafting or moderate aortic insufficiency is present. Special attention to cannulation techniques, perfusion conditions, valve exposure, and de-airing maneuvers are all important to ensure good clinical results. Using a tailored approach we have performed mitral valve repair in 22 patients with a patent left internal mammary artery graft following coronary artery bypass grafting between July 1992 and February 2000 with acceptable morbidity and low mortality.

Adult↗

An engineering model of dynamic cardiomyoplasty. II. Clinical applications.

Previously, a modification to the Sunagawa engineering model for the isolated left ventricle and arterial system was proposed and validated for dynamic cardiomyoplasty in an acute goat preparation. To test the hypothesis that this model may be applied to the clinical scenario in cardiomyoplasty patients, we predicted human stroke volume using the model with human clinical data from the literature. Predicted stroke volume correlated well with published stroke volume in patients who have had the dynamic cardiomyoplasty procedure. These results suggest that the modest hemodynamic improvement commonly reported after the procedure is performed may be due to diminished latissimus dorsi strength after transformation. The validity of both the original Sunagawa model and the previously proposed modification for dynamic cardiomyoplasty is further supported with these results. A nomogram methodology for predicting stroke volume after dynamic cardiomyoplasty for any particular patient is presented.

Biomechanical Phenomena↗

An engineering model of dynamic cardiomyoplasty. I.

Dynamic cardiomyoplasty (DCM) is an emerging surgical procedure for heart failure in which the patient's latissimus dorsi (LD) muscle is wrapped around the heart and stimulated to contract in synchrony with the heartbeat as a cardiac assist measure. A 6 week training protocol of progressive electrical stimulation renders the normally fatigueable skeletal muscle fatigue-resistant and suitable for chronic stimulation. To date, over 500 procedures have been performed in worldwide clinical trials. Investigators typically report symptomatic improvement and modest hemodynamic improvement in patients. Controversy exists regarding the exact mechanism of DCM. To test the hypothesis that DCM augments cardiac stroke volume through improvement in systolic function, we formulated an engineering model of dynamic cardiomyoplasty to predict stroke volume. The heart and the LD were modeled as nested (series) elastance chambers, and the vasculature was represented by a two-element Windkessel model. Using five healthy goats, we verified model predictions of stroke volume for both stimulator ON beats (y = 1.00x-0.08, r = 0.87, p < 0.0001) and OFF beats (y = 1.01x+1.06, r = 0.91, p < 0.0001), where x and y are the measured and predicted stroke volumes, respectively. The model confirms that using untrained latissimus dorsi applied to the normal myocardium produces only moderate increases in stroke volume and suggests that future research should focus on increasing LD strength after training.

Cardiomyoplasty↗