Search PubMed⌕ Search

Biomedical subjects

R M Savage

Publications and source records attributed to R M Savage.

At least 19 recordsLinked to original sources
PubMed2001

A polychaete hunchback ortholog.

We report the first characterization of a segmentation gene homologue in the basal polychaete Capitella capitata using a pan-annelid cross-species antibody to the hunchback-like gene product. In flies, the gap segmentation gene hunchback (hb) encodes a C(2)H(2) zinc-finger transcription factor that plays a pivotal role in patterning the anterior region of the fly body plan. The hb orthologue in Capitella (Cc-hb) is expressed maternally and in all micromere and macromere cells throughout cleavage. At gastrulation, nuclear Cc-hb protein is expressed in the micromere-derived surface epithelium that undergoes epiboly and in the large vegetal blastomeres that gradually become internalized. During organogenesis, Cc-hb is expressed in the developing gut epithelium, the prostomial and pygidial epithelium, and in a subset of differentiated neurons in the adult central nervous system. Cc-hb is not expressed in the segmental precursor cells in the trunk. The Cc-hb expression domains in Capitella are similar to those reported for the leech hb orthologue (LZF2), and many of the observed differences between the annelid classes correlate with changes in life history. The lack of detectable annelid hb protein in the trunk at the time of AP pattern formation in leech and in polychaete suggests that the anterior organizing function of hb in flies originated in the arthropod or insect lineage.

Amino Acid Sequence↗
PubMed2000

The leech hunchback protein is expressed in the epithelium and CNS but not in the segmental precursor lineages.

We are interested in identifying the regulatory genes involved in segmental pattern formation in annelids. The Drosophila segmentation gene hunchback (hb) is critical for the proper anteroposterior development of the fly embryo, but its function outside the diptera is currently unknown. Here, the protein expression pattern of Leech Zinc Finger II (LZF2), a leech orthologue of hb is characterized. In early embryogenesis, LZF2 protein is expressed in a subset of micromeres and is later expressed in the micromere-derived epithelium of the provisional epithelium and prostomium. LZF2 protein is detected in the ventral nerve cord during organogenesis, first in interganglionic muscle cells and later in subsets of neurons in each neuromere of the CNS. The location of immunoreactive cells during development and the similarity of the expression pattern of LZF2 to the expression of the Caenhorhabditis elegans hb homologue hbl-1 suggests that LZF2 plays a role in the morphogenetic movements of leech gastrulation and later in CNS specification but not in anteroposterior pattern formation.

Animals↗
PubMed2000

Clinical utility of echocardiography in the management of implantable ventricular assist devices.

BACKGROUND: The high mortality rate of congestive cardiac failure, the cost and complications of cardiac transplantation, and the waiting list mortality rate resulting from donor organ scarcity have encouraged the development of surgical techniques as bridges to transplantation or as long-term palliative therapy. Implantable left ventricular assist devices are now routinely used as such a bridge, and within the REMATCH Trial, as permanent palliative devices in nontransplant candidates. These are mechanical managements with myriad mechanical complications and pitfalls. Echocardiography has been extensively used in our institution to detect and diagnose previously documented and hitherto unencountered complications of these procedures. METHODS AND RESULTS: The role of echocardiography in these procedures, including preoperative patient selection, intraoperative transesophageal echocardiography, and postoperative troubleshooting and late follow-up, is discussed. We describe our clinical echocardiographic approach, which has developed over 91 assist-device procedures. The relative frequency and clinical impact of specific anatomic, physiologic, hemodynamic, and mechanical features are described. New techniques such as the Doppler quantification of assist device inflow obstruction are illustrated, as are the device cannula position, the detection of device valve failure, and the parameters related to the remodeling procedure. CONCLUSIONS: Echocardiography in heart failure surgery has proved to be an invaluable tool in the diagnosis and management of mechanical complications. The experience gained in our institution may serve as an aid to new surgical programs treating these critically ill patients.

Echocardiography↗
PubMed2000

Management strategies for high-risk cardiac surgery: improving outcomes in patients with heart failure.

BACKGROUND: Surgical heart failure management is the fastest growing aspect of cardio-vascular surgery. Advances in cardiac surgical techniques have changed the number and types of operations permitted physicians and thus broadened the complexity of patients recommended for operation. METHODS: Surgeons, anesthesiologists and cardiologists face hemodynamic and patho-physiological challenges that can be optimally overcome only by modifying treatment strategies. Because many treatment standards are still evolving in this rapidly advancing field, a team of cardiovascular surgeons and anesthesiologists convened to share clinical experience and impressions and discuss practical issues related to high-risk patients undergoing heart surgery. RESULTS: Heart failure pathophysiology, surgical heart failure management, including mitral reconstruction and left ventricular remodeling, cardiopulmonary bypass weaning, inotropic support, transesophageal echocardiography and acute cardiovascular collapse after cardiac surgery are discussed. CONCLUSION: This article is intended to guide clinicians to improve patient care and outcomes in this special population by providing specific guidance on the appropriate use of inotropic and mechanical support in patients undergoing high-risk procedures using innovative techniques.

Cardiac Surgical Procedures↗
PubMed1999

MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content.

PURPOSE: To determine the transverse relaxation rates R2 and R2' from several gray matter regions and from frontal cortical white matter in healthy human brains in vivo and to determine the relationship between relaxation rates and iron concentration [Fe]. MATERIALS AND METHODS: Six healthy adults aged 19-42 years underwent thin-section gradient-echo sampling of free induction decay and echo magnetic resonance (MR) imaging at 3.0 T. Imaging covered the mesencephalon and basal ganglia. RESULTS: Relaxation rates (mean +/- SD) were highest in globus pallidus (R2 = 25.8 seconds-1 +/- 1.1, R2' = 12.0 seconds-1 +/- 2.1) and lowest in prefrontal cortex (R2 = 14.4 seconds-1 +/- 1.8, R2' = 3.4 seconds-1 +/- 1.1). Frontal white matter measurements were as follows: R2 = 18.0 seconds-1 +/- 1.2 and R2' = 3.9 seconds-1 +/- 1.2. For gray matter, both R2 and R2' showed a strong correlation (r = 0.92, P < .001 and r = 0.90, P < .001, respectively) with [Fe]. Although the slopes of the regression lines for R2' versus [Fe] and for R2 versus [Fe] were similar, the iron-independent component of R2' (2.2 seconds-1 +/- 0.6), the value when [Fe] = 0, was much less than that of R2 (12.7 seconds-1 +/- 0.7). CONCLUSION: The small iron-independent component R2', as compared with that of R2, is consistent with the hypothesis that R2' has higher iron-related specificity.

Adult↗
PubMed1997

Left ventricular diastolic filling with an implantable ventricular assist device: beat to beat variability with overall improvement.

OBJECTIVES: We studied the effects of left ventricular (LV) unloading by an implantable ventricular assist device on LV diastolic filling. BACKGROUND: Although many investigators have reported reliable systemic and peripheral circulatory support with implantable LV assist devices, little is known about their effect on cardiac performance. METHODS: Peak velocities of early diastolic filling, late diastolic filling, late to early filling ratio, deceleration time of early filling, diastolic filling period and atrial filling fraction were measured by intraoperative transesophageal Doppler echocardiography before and after insertion of an LV assist device in eight patients. A numerical model was developed to simulate this situation. RESULTS: Before device insertion, all patients showed either a restrictive or a monophasic transmitral flow pattern. After device insertion, transmitral flow showed rapid beat to beat variation in each patient, from abnormal relaxation to restrictive patterns. However, when the average values obtained from 10 consecutive beats were considered, overall filling was significantly normalized from baseline, with early filling velocity falling from 87 +/- 31 to 64 +/- 26 cm/s (p < 0.01) and late filling velocity rising from 8 +/- 11 to 32 +/- 23 cm/s (p < 0.05), resulting in an increase in the late to early filling ratio from 0.13 +/- 0.18 to 0.59 +/- 0.38 (p < 0.01) and a rise in the atrial filling fraction from 8 +/- 10% to 26 +/- 17% (p < 0.01). The deceleration time (from 112 +/- 40 to 160 +/- 44 ms, p < 0.05) and the filling period corrected by the RR interval (from 39 +/- 8% to 54 +/- 10%, p < 0.005) were also significantly prolonged. In the computer model, asynchronous LV assistance produced significant beat to beat variation in filling indexes, but overall a normalization of deceleration time as well as other variables. CONCLUSIONS: With LV assistance, transmitral flow showed rapidly varying patterns beat by beat in each patient, but overall diastolic filling tended to normalize with an increase of atrial contribution to the filling. Because of the variable nature of the transmitral flow pattern with the assist device, the timing of the device cycle must be considered when inferring diastolic function from transmitral flow pattern.

Adult↗
PubMed1997

Intraoperative echocardiography is indicated in high-risk coronary artery bypass grafting.

BACKGROUND: Intraoperative echocardiography is a valuable monitoring and diagnostic technology used in cardiac surgery. This reports our clinical study of the usefulness of intraoperative echocardiography to both surgeons and anesthesiologists for high-risk coronary artery bypass grafting. METHODS: From March to November 1995, 82 consecutive high-risk patients undergoing coronary artery bypass grafting were studied in a four-stage protocol to determine the efficacy of intraoperative echocardiography in management planning. Alterations in surgical and anesthetic/hemodynamic management initiated by intraoperative echocardiography findings were documented in addition to perioperative morbidity and mortality. RESULTS: Intraoperative echocardiography initiated at least one major surgical management alteration in 27 patients (33%) and at least one major anesthetic/hemodynamic change in 42 (51%). Mortality and the rate of myocardial infarction in this consecutive high-risk study population using intraoperative echocardiography and in a similar group of patients without the use of intraoperative echocardiography was 1.2% versus 3.8% (not significant) and 1.2% versus 3.5% (not significant), respectively. CONCLUSIONS: We conclude that when all of the isolated diagnostic and monitoring applications of perioperative echocardiography are routinely and systematically performed together, it is a safe and viable tool that significantly affects the decision-making process in the intraoperative care of high-risk patients undergoing primary isolated coronary artery bypass grafting and may contribute to the optimal care of these patients.

Aged↗
PubMed1996

Prediction of right ventricular dysfunction after left ventricular assist device implantation.

BACKGROUND: Right ventricular dysfunction (RVD) significantly affects mortality and morbidity after left ventricular assist device (LVAD) implantation, and its occurrence often is unpredictable. The aim of the present study was to identify predictors of RVD after LVAD implantation. METHODS AND RESULTS: We studied right ventricular (RV) hemodynamics in 28 patients before and after LVAD implantation with a rapid-response thermistor pulmonary artery catheter. Measurements included mean right atrial pressure (RAP), mean pulmonary arterial pressure (PAP), cardiac index, transpulmonary gradient (TPG), pulmonary vascular resistance (PVR), RV end-diastolic and end-systolic volume indexes (EDVI and ESVI, respectively), and RV ejection fraction (RVEF). We regarded patients who had RAP > or = 15 mm Hg at LVAD explantation (n = 8) or who required an RV assist device (n = 3) as the RVD group (n = 11). The other patients were categorized as the RV nondysfunctional group (RVN, n = 17). Before LVAD implantation, the RVD group had larger RV volumes (200 +/- 107 versus 125 +/- 46 mL/m2 for EDVI; 177 +/- 109 versus 104 +/- 48 mL/m2 for ESVI) and higher preload (23 +/- 6 versus 17 +/- 6 mm Hg for RAP) and afterload (20 +/- 9 versus 13 +/- 6 mm Hg for TPG; 5.9 +/- 3.0 versus 3.8 +/- 2.0 Wood units for PVR) than the RVN group (P < .05 for all). RVEF and PAP did not differ significantly. LVAD implantation remarkably improved RV hemodynamics in both groups, decreasing RV volumes, preload, and afterload and increasing RVEF in all patients, but post-LVAD PAP tended to be higher in the RVD group. Multivariate logistic regression analysis revealed that RAP and TPG before LVAD implantation and an acute decrease (delta) in PAP by LVAD were significant predictors of RVD (P < .05). The sensitivity for predicting RVD by a combination of at least two of these three predictors (RAP > or = 20 mm Hg, TPG > or = 16 mm Hg, and delta PAP < or = 10 mm Hg) was 82%, and the specificity was 88%. CONCLUSIONS: Dilated right ventricle with increased RV preload and afterload predisposes to RVD after LVAD implantation. Not only baseline parameters but also the immediate hemodynamic response to the LVAD are predictive, and a combination of these parameters may be useful in predictions of the occurrence of RVD after LVAD implantation.

Adult↗
PubMed1996

Identification and characterization of a hunchback orthologue, Lzf2, and its expression during leech embryogenesis.

Lzf1 and Lzf2 are leech zinc finger (Lzf) genes that are shown to be orthologues to the Drosophila gap gene hunchback (hb). Neither in situ hybridization nor RT-PCR detected Lzf1 transcripts in leech embryos or adults. Lzf2 expression was examined in leech embryos at various stages by in situ hybridization. Lzf2 is expressed continually throughout the early embryonic cleavage divisions, including the period during which the embryo forms stem cells that will give rise to the segmented tissues of the adult. At the time of segmental pattern formation, Lzf2 RNA is expressed uniformly along the length of the segmented trunk in both the ectodermal and mesodermal tissues. This is in contrast to the anteriorly restricted gradient of hb RNA shown to be critical to the normal anteroposterior (AP) patterning of the insect embryo. Thus, this leech orthologue of hb does not appear to play a comparable role in the patterning of the AP axis. In addition, Lzf2 is expressed during organogenesis in segmentally restricted patterns in the central nervous system, the gut, and epidermally derived structures. Lzf2 is the first hb orthologue to be characterized in detail outside of insects and its expression pattern suggests that hb may have acquired a gap gene function in arthropods or insects after their phyletic separation from the annelids.

Amino Acid Sequence↗
PubMed1996

Left ventricular echocardiographic and histologic changes: impact of chronic unloading by an implantable ventricular assist device.

OBJECTIVES: We studied the effects of chronic left ventricular unloading by a ventricular assist device and assessed left ventricular morphologic and histologic changes. BACKGROUND: The implantable left ventricular assist device has been effective as a "bridge" to cardiac transplantation. Although there are reports documenting its circulatory support, little is known about the effects of chronic left ventricular unloading on the heart itself. METHODS: We performed intraoperative transesophageal echocardiography at the insertion and explanation of a HeartMate left ventricular assist device in 19 patients with end-stage heart failure. They were supported by the assist device for 3 to 153 days (mean [+/-SD] 68 +/- 33). Measurements were taken retrospectively to obtain left atrial and ventricular diameters and interventricular septal and posterior wall thicknesses. Histologic examinations were made from the left ventricular myocardial specimens of 15 patients at the times of insertion and explanation for heart transplantation. Insertion and explanation specimens were compared qualitatively (0 to 3 scale) for wavy fibers, contraction band necrosis and fibrosis, with quantitative measurement of minimal myocyte diameter across the nucleus. RESULTS: Left atrial and left ventricular diastolic and systolic diameters decreased immediately after insertion of the left ventricular assist device (from 46 to 35, 63 to 41 and 59 to 36 mm, respectively, all p < 0.001). Left ventricular wall thickness increased from 10 to 14 mm (p < 0.001) for the interventricular septum and from 10 to 13 mm for the posterior wall (p<0.001). No echocardiographic measurements showed significant subsequent changes at the chronic stage. Myocardial histologic findings demonstrated a reduction in myocyte damage (from 1.9 to 0.5, p<0.001, for wavy fiber and from 1.3 to 0.2, p<0.01, for contraction band necrosis) and an increase in fibrosis (from 1.3 to 1.9, p<0.05), but without significant change in myocyte diameter (from 15.6 to 16.8 micrometer, p=0.065). CONCLUSIONS: Left ventricular unloading with the implantable assist device induces an immediate increase in wall thickness, consistent with the reduction in chamber size, thereby decreasing wall stress. Chronic unloading allows myocardial healing and fibrosis without evidence for ongoing myocyte damage or atrophy. Left ventricular assist device insertion may have a role in "resting" the ventricle for selected patients with heart failure.

Adult↗
PubMed1995

Structural and left ventricular histologic changes after implantable LVAD insertion.

Long-term support on the implantable left ventricular assist device (LVAD) produces structural changes in the recipient's heart. To assess the possibility of heart "recovery" we reviewed the records of 19 HeartMate LVAD recipients to determine structural and left ventricular histologic changes during LVAD support. Intraoperative transesophageal echocardiographic studies were performed in the operating room before LVAD insertion, immediately after LVAD insertion, and at explantation and heart transplantation (mean duration of support, 76 +/- 34 days). The initiation of LVAD pumping led to an immediate decrease (p < 0.001) in left ventricular dimensions, which were not significantly different by the time of device explantation. Left ventricular fractional shortening did not significantly improve during LVAD support (0.07 +/- 0.03 before LVAD; 0.11 +/- 0.10 immediately after LVAD; 0.11 +/- 0.11 before explantation). Histologic specimens showed a significant reduction in the number of wavy fibers, and contraction band necrosis (p < 0.01), both markers of acute myocyte damage. However, myocardial fibrosis increased (p < 0.05). Myocyte diameter increased slightly (p = 0.07). We conclude that implantable LVAD support is associated with immediate changes in ventricular structure. Histologic markers of acute myocyte damage improve, but fibrosis increases. Because the structural changes occur immediately, they do not indicate "recovery" of left ventricular function, but merely changes in loading conditions.

Adult↗
PubMed1995

Hemodynamic and physiologic changes during support with an implantable left ventricular assist device.

To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy.

Adult↗