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Biomedical subjects

Isaac George

Publications and source records attributed to Isaac George.

9 recordsLinked to original sources
PubMed2006

Effect of passive cardiac containment on ventricular synchrony and cardiac function in awake dogs.

OBJECTIVE: Passive restraint of the left ventricle (LV) has been shown to have beneficial effects on acute hemodynamics and reverse remodeling in both animal and human models. The goals of this study were to test whether a left ventricular support device (LVSD) improves LV synchrony and/or affects cardiac performance. METHODS: Ten dogs were chronically instrumented to measure hemodynamics and LV volume (sonomicrometry). Congestive heart failure (CHF) was induced by repeated intracoronary microembolization via a chronically implanted coronary catheter. The LVSD was implanted after establishment of CHF in five animals, and five animals were observed as controls. All animals were then observed for 8 weeks. A mathematical model to measure LV synchrony was used to evaluate LV motion over time. RESULTS: Mean arterial pressure and LV pressures was significantly increased after LVSD therapy, and LV pressure-volume relationships were shifted leftwards, although no change was seen in ejection fraction, end-systolic elastance, or LV dP/dt versus control. There was no significant change in diastolic function in LVSD animals compared with control animals. End-diastolic volumes were reduced by 15% after 8 weeks with LVSD treatment, versus an increase of 8% in control animals (p<0.05). Synchrony was significantly improved with LVSD therapy compared with control (9% vs 76% of baseline) in 1 of 11 ventricular dimension axes (Anterior-Apex). CONCLUSIONS: LVSD therapy provided only minimal improvement in ventricular synchrony and partially improved hemodynamics. Further study into mechanisms of benefit are warranted.

Animals↗
PubMed2006

A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia.

The purpose of this study was to test if HBOC-201, a hemoglobin-based oxygen-carrying solution, can decrease infarct size (or Inf) during acute, severe myocardial ischemia and reperfusion. To test the impact of HBOC-201 on infarct size, ischemia was produced in 18 dogs by coronary stenosis to achieve 80-95% flow reduction for 195 min along with pacing 10% above the spontaneous heart rate, followed by 180 min of reperfusion. Animals were randomized to intravenous infusion of HBOC-201 (1 g/kg) (n=6), normal saline (NS) (n=6), or phenylephrine (Phe) (n=6, as a control for the increased blood pressure seen with HBOC-201), given 15 min after the start of ischemia. Amount of infarct was quantified as the ratio between area at risk (AAR) and Inf after Evans blue and 2,3,5-triphenyltetrazolium chloride staining. Hearts were divided into five layers from base (layer A) to apex (layer E) and photographed for digital image analysis of AAR and Inf. Regional myocardial function (RMF) was also measured after 60 min of ischemia and 15 min of reperfusion. Inf/AAR was significantly reduced after HBOC-201 therapy (4.4+/-2.2%) vs. NS (26.0+/-3.6%) and Phe (25.7+/-4.1%) (both, P<0.05). RMF after reperfusion was restored to 92% of baseline with HBOC-201 compared with 11% of baseline after NS (P<0.05) and 49% after Phe (P=not significant). HBOC-201 administration after induction of severe myocardial ischemia by acute coronary stenosis reduces infarct size and improves myocardial viability.

Animals↗
PubMed2006

Predictors and outcomes of continuous veno-venous hemodialysis use after implantation of a left ventricular assist device.

BACKGROUND: Post-operative renal failure is a common complication after left ventricular assist device (LVAD) implantation. This study was designed to evaluate predictors and outcomes of acute renal failure after LVAD insertion. METHODS: Two-hundred one patients undergoing LVAD implantation at a single institution from June 1996 through April 2004 were retrospectively analyzed. Patients were categorized into 2 groups: those who required post-operative continuous veno-venous hemodialysis (CVVHD) (Group 1, n = 65, 32.3%) and those who did not (Group 2, n = 136, 67.7%). Independent predictors of post-operative renal failure requiring CVVHD were determined using multivariate logistic regression techniques. RESULTS: Patients who had post-operative renal failure requiring CVVHD were older (53.7 +/- 12.9 vs 48.2 +/- 14.2 years, p = 0.009), had a higher incidence of intra-aortic balloon pump use (46.6% vs 26.2%, p = 0.006), and had a higher pre-operative mean LVAD score (5.8 +/- 3.5 vs 3.8 +/- 3.3, p = 0.001) than those without renal failure. LVAD score was the only independent predictor of post-operative renal failure requiring CVVHD (odds ratio = 1.226, p = 0.006). Sepsis rate was higher (33.3% vs 6.9%, p < 0.001) and bridge-to-transplantation rate was lower (52.4% vs 83.5%, p < 0.001) in Group 1 than in Group 2. Post-LVAD survival rates at 1, 3, 5 and 7 years for Group 1 and Group 2 were 43.2%, 39.1%, 34.7% and 34.7% vs 79.2%, 74.0%, 68.3% and 66.4%, respectively (log rank, p < 0.001). CONCLUSIONS: Acute renal failure necessitating CVVHD remains a serious complication after LVAD and confers significant morbidity and mortality. Pre-operative evaluation of patient risk factors and optimization of peri-operative hemodynamics are of utmost importance to prevent this major complication.

Acute Kidney Injury↗
PubMed2006

Clinical indication for use and outcomes after inhaled nitric oxide therapy.

BACKGROUND: Inhaled nitric oxide (iNO) use is widespread, but the long-term outcomes after therapy in adult patients remain unknown. METHODS: All 376 patients receiving perioperative iNO (excluding pediatric and interventional cardiology procedures) at Columbia University Medical Center were prospectively followed from 2000 to 2003. Survival data were collected from chart review. RESULTS: Inhaled nitric oxide was used to treat pulmonary and right ventricular failure in patients undergoing orthotopic heart transplantation (OHT, n = 67), orthotopic lung transplantation (n = 45), cardiac surgery (n = 105), and ventricular assist device placement (n = 66), and for hypoxemia in other surgery (n = 34) and medical patients (n = 59). Average follow-up was 2.9 +/- 1.0 years. Overall mortality was lowest when iNO was used after OHT (25.4%) and orthotopic lung transplantation (37.8%), intermediately after cardiac surgery (61%), ventricular assist device (62%), and other surgery patients (75%), and highest among medical patients (90%; all p < 0.005). The cost of iNO therapy was lower in transplantation versus medical patients, with a trend toward shorter duration of use. In multivariate analysis, respiratory failure and use in non-OHT were independent predictors of mortality (both p = 0.001). A risk score greater than 1 (score = non-OHT use 1, plus right ventricular failure 1) predicted a mortality of 76.5% versus 37.2% (p < 0.001). CONCLUSIONS: Use of iNO for pulmonary hypertension in patients undergoing OHT and orthotopic lung transplantation was associated with a significantly lower overall mortality rate compared with its use after cardiac surgery or for hypoxemia in medical patients. Inhaled nitric oxide does not appear to be cost effective when treating hypoxemia in medical patients with high-risk scores and irreversible disease.

Administration, Inhalation↗
PubMed2006

Effect of clenbuterol on cardiac and skeletal muscle function during left ventricular assist device support.

BACKGROUND: High-dose clenbuterol (a selective beta2-adrenergic agonist) has been proposed to promote myocardial recovery during left ventricular assist device (LVAD) support, but its effects on cardiac and skeletal muscle are largely unknown. METHODS: Seven subjects with heart failure (5 ischemic, 2 non-ischemic) were started on oral clenbuterol 5 to 46 weeks post-LVAD implantation and up-titrated to daily doses of 720 microg. The following procedures were performed at baseline and after 3 months of therapy: echocardiography at reduced support (4 liters/min); cardiopulmonary exercise testing; body composition analysis; and quadriceps maximal voluntary contraction (MVC). Myocardial histologic analysis was measured at device implantation and explantation. RESULTS: There were no serious adverse events or arrhythmias. Creatine phosphokinase (CPK) was elevated in 4 subjects, with no clinical sequelae. No change in ejection fraction was seen. End-diastolic dimension increased significantly (4.73 +/- 0.67 vs 5.24 +/- 0.66; p < 0.01), despite a trend toward increased LV mass. Body weight and lean mass increased significantly (75.5 +/- 17.9 vs 79.2 +/- 25.1 kg, 21.1 +/- 8.9 vs 23.6 +/- 9.7 kg, respectively; both p < 0.05). Exercise capacity did not change, but MVC improved significantly from 37.0 +/- 15.7 to 45.8 +/- 20.6 kg (p < 0.05). No significant change in myocyte size or collagen deposition was seen. CONCLUSIONS: Cardiac function did not improve in this cohort of LVAD patients treated with high-dose clenbuterol. However, clenbuterol therapy increased skeletal muscle mass and strength and prevented the expected decrease in myocyte size during LVAD support. Further study will clarify its potential for cardiac and skeletal muscle recovery.

Adrenergic beta-Agonists↗
PubMed2006

Adult-age donors offer acceptable long-term survival to pediatric heart transplant recipients: an analysis of the United Network of Organ Sharing database.

OBJECTIVES: A critical shortage of donor organs has caused many centers to use less restrictive donor criteria, including the use of adult-age donors for pediatric recipients. The purpose of this study is (1) to describe the supply of pediatric (0-18 years) heart donors, (2) to explore the relationship between donor age and long-term survival, and (3) to define threshold age ranges associated with decreased long-term survival. METHODS: The United Network of Organ Sharing provided deidentified patient-level data. Primary analysis focused on 1887 heart transplant recipients aged 9 to 18 years undergoing transplantation from October 1, 1987, to September 25, 2005. Kaplan-Meier analysis and log-rank tests were used in time-to-event analysis. Receiver operating characteristic curves and stratum-specific likelihood ratios were generated to compare survival at various donor age thresholds. RESULTS: The number of pediatric donors decreased (P < .001) over the study period, particularly from 1993 (n = 640) through 2004 (n = 432). Among recipients aged 9 to 18 years, univariate analysis demonstrated a statistically significant (P < .001) inverse relationship between donor age and survival. Stratum-specific likelihood ratio analysis generated 3 strata for donor age: the low-risk, intermediate-risk, and high-risk groups consisted of donors aged 13 years or younger (n = 611, 32.41%), 14 to 51 years (n = 1258, 66.7%), and 52 years and older (n = 16, 0.85%), respectively. In the low-risk, intermediate-risk, and high-risk groups median survival was 4069 days (11.1 years), 3495 days (9.57 years), and 1197 days (3.28 years), respectively. CONCLUSIONS: Although donors aged 13 years or less offer pediatric recipients the best chance for achieving long-term survival, donors aged 14 to 51 years offer good outcomes to pediatric recipients. Consideration should be given to expanded use of well-selected adult-age donors for pediatric recipients.

Adolescent↗
PubMed2006

Direct left ventricle-to-coronary artery stent restores perfusion to chronic ischemic swine myocardium.

BACKGROUND: Direct left ventricle (LV)-to-coronary artery shunts (VSTENT) have been proposed as an alternative means of myocardial revascularization. The goal of this study was to examine quantitative changes in myocardial perfusion and possible mechanisms of revascularization with an LV-to-coronary shunt. METHODS: Ameroid occluders were implanted on the proximal left anterior descending coronary artery (LAD) of 6 pigs to create chronic ischemia. Four weeks later, a VSTENT was placed to directly connect the distal LAD with the LV chamber. Animals survived for an additional 3 weeks and received periodic bromodeoxyuridine (BrdU) injections to identify dividing cells to identify and quantify angiogenesis. Regional myocardial perfusion (RMP) was measured with color microspheres under adenosine vasodilatory stress before and 3 weeks after VSTENT implantation. Vascularity was assessed histologically by an overall vascularity index and a growth index reflecting the density of BrdU-positive vascular cells. RESULTS: Three weeks after VSTENT placement, RMP improved from 38.4% +/- 19.6% of non-ischemic flow to 86.8% +/- 13.7% in treated animals (P < .05). This benefit was accompanied by histological evidence of increased vascularity and vascular proliferation. Four of 5 animals had patent and functional devices at the end of the study. CONCLUSION: Chronic VSTENT placement improves RMP and may promote arterial remodeling in chronically ischemic porcine myocardium.

Animals↗