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Biomedical subjects

A S Wechsler

Publications and source records attributed to A S Wechsler.

At least 19 recordsLinked to original sources
PubMed2001

Management of acute cardiac failure with mechanical assist: experience with the ABIOMED BVS 5000.

BACKGROUND: Mechanical circulatory assist industries have developed ventricular assist devices (VAD) for short-, intermediate-, and long-term use. The purpose of this report is to describe the progress made with the ABIOMED Biventricular System (BVS) 5000 (ABIOMED, Inc, Danvers, MA) short-term VAD. METHODS: From June 1994 through August 2000, all cardiogenic shock patients who required short-term mechanical assist were supported with the ABIOMED BVS 5000. Insertion criteria included any condition that may potentially result in cardiac recovery. A formal algorithm for timing of insertion was established to standardize implantation criteria. RESULTS: A total of 45 patients were supported at Hahnemann University Hospital, Philadelphia, PA. There were 26 male and 19 female patients, with a mean age of 57.9 years (range 33 to 80 years). Devices were inserted for postcardiotomy shock in 36 patients (80%) and precardiotomy shock in 9 patients (20%). The average duration of support was 8.3 days (range 1 to 31 days). Overall, there were 22 (49%) patients weaned from support and 14 (31%) discharged from the hospital. For patients in whom the device was implanted in accordance with an established protocol (group A), the wean and discharge rates were 60% and 43%, respectively. The most common morbidities included bleeding and adverse neurologic events. CONCLUSIONS: The ABIOMED BVS 5000 VAD continues to be a valuable form of short-term mechanical assist for acute cardiogenic shock. The formation of a uniform VAD insertion algorithm has helped to standardize protocols in management.

Acute Disease↗
PubMed2001

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Humans↗
PubMed2000

Early detection of acute allograft rejection by linear and nonlinear analysis of heart rate variability.

OBJECTIVE: The first months after orthotopic heart transplantation are associated with the highest risk of acute allograft rejection. This study explores the utility and reliability of linear and novel nonlinear metrics of heart rate variability as predictors of graft rejection. The underlying hypothesis is that the transplanted heart, in response to inflammatory mediators, alters the dynamic properties of its rhythm-generating system. METHODS: In a cross-sectional study of 45 patients who had undergone heart transplantation, spanning a period of 4 months after the operation, heart rate variability was examined by time- and frequency-domain analysis. The nonlinear features of heart rate variability were studied by computing a pointwise correlation dimension of R-R interval time series. The results of heart rate variability analysis were compared with those of endomyocardial surveillance biopsy studies using the International Society for Heart and Lung Transplantation scoring system. RESULTS: Duration of heart transplantation itself exhibited a significant (P<.05) association with the onset of rejection. Specific predictors of acute rejection based on heart rate variability were identified, including shortening of the R-R interval (from 700 +/- 68 to 648 +/- 72 ms), an increase in the ratio of low-frequency (0.04-0.15 Hz) to high-frequency (0.15-0.40 Hz) spectral power (from 0.3 +/- 0.2 to 0.6 +/- 0.4), and a decrease in pointwise correlation dimension values (from 1.7 +/- 0.7 to 0.9 +/- 0.3 units). Multivariable logistic regression analysis (R (2) = 0.4) revealed that the only significant independent risk predictors were pointwise correlation dimension (odds ratio, 2.2 per 0.1 unit) and duration of heart transplantation (odds ratio, 1.7 per week). CONCLUSION: Nonlinear measures of heart rate variability provide noninvasive means for identifying patients undergoing cardiac transplantation with acute rejection, thereby enabling the assessment of the time-dependent adaptive response of the donor heart to its host.

Adult↗
PubMed1999

Hyperdynamic circulation of arteriovenous fistula preconditions the heart and limits infarct size.

BACKGROUND: Chronic arteriovenous fistulae (AVF) create sustained hyperdynamic circulation. It is not known whether hyperdynamic circulation alters myocardial sensitivity to ischemia and reperfusion injury. We tested the hypothesis that AVF activate molecular responses that increase tolerance to infarction in dogs. METHODS: Twelve dogs were divided into two groups: 1) AVF group, where an AVF in the femoral region was done; and 2) sham-operated group (each n = 6). After 8 weeks, left ventricular performance was determined from stroke work/end-diastolic length relationship. Myocardial biopsy was obtained to determine heat-shock protein 70 and adenosine triphosphate (ATP) pool. Left anterior descending coronary artery was occluded for 90 minutes at 37 degrees C, followed by 4 hours of reperfusion. Coronary blood flow was determined using different colored microspheres. RESULTS: The fistula group showed improvement of left ventricular performance (p = 0.03). The infarct size was significantly lower in the fistula group; it was 9.2+/-2.0% in the fistula group versus 28.4+/-5.2% in the sham group (p < 0.05). ATP depletion during ischemia was less in the fistula group (p = 0.02). Regional myocardial blood flow was significantly higher in the fistula group (p = 0.03). CONCLUSIONS: Peripheral AVF improve the left ventricular performance, and decrease infarct size and ATP depletion. This protective effect is caused by the development of collaterals in the coronary circulation without expression of heat-shock protein 70.

Adenosine Triphosphate↗
PubMed1999

Coronary artery disease in identical twins.

The incidence of coronary artery disease in identical twins is unknown. The knowledge of ischemic heart disease in this patient population is represented by case reports. There is considerable controversy regarding the environmental and genetic factors that play a role in the pathogenesis of this disorder. The natural history of coronary artery disease in an asymptomatic twin with a symptomatic counterpart is unclear. We present a case report and literature review of coronary artery disease in identical twins. On the basis of our patient and the information of other patients, asymptomatic twins of symptomatic counterparts require aggressive assessment and management for occult coronary artery disease.

Aged↗
PubMed1999

Phenylephrine induces delayed cardioprotection against necrosis without amelioration of stunning.

BACKGROUND: Alpha-adrenergic stimulation induces protection in reperfused ischemic (I/R) myocardium 24 hours later. We tested the hypothesis that phenylephrine improves dysfunction after global I/R by limiting cell death not stunning. METHODS: Rabbits were pretreated with either phenylephrine or vehicle. Twenty-four hours later, isolated hearts underwent either 45 (infarction protocol) or 20 minutes (stunning protocol) of global ischemia before 2 hours of reperfusion (n = 6 per group). Cell death was determined by triphenyl tetrazolium chloride staining (infarction) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) (apoptosis). RESULTS: Compared with vehicle, phenylephrine pretreatment improved post-I/R-developed pressures in hearts after infarction (53.2 +/- 4.0 vs 35.8 +/- 4.1 mm Hg, p = 0.01) but not stunning protocol (64.3 +/- 8.9 vs 57.7 +/- 6.2 mm Hg, p = NS). The improved developed pressure was due to better diastolic recovery. Systolic pressures were similar between groups. Phenylephrine markedly decreased infarction (9.0 +/- 1.9% vs 40.8 +/- 1.8% for vehicle, p < 0.001) and TUNEL-positive staining. Stunned hearts of either group had less than 3% infarction and no apoptosis. CONCLUSIONS: Phenylephrine pretreatment 24 hours before global I/R improves function by limiting infarction but not stunning.

Animals↗
PubMed1999

Absence of vasospasm in radial artery CABG on high-dose norepinephrine.

One of the concerns in using radial artery as coronary artery bypass grafts centers around its unusual propensity for vasospasm when experimentally exposed to norepinephrine. This case report demonstrates an absence of vasospasm in a radial artery graft on high dose norepinephrine and may provide reassurance when alpha-agonists are required in this setting.

Coronary Artery Bypass↗
PubMed1999

Delayed myocardial preconditioning by alpha1-adrenoceptors involves inhibition of apoptosis.

OBJECTIVE: Previous studies have demonstrated that alpha1-adrenoceptor activation increases myocardial resistance to ischemic injury 24 hours later. Here we tested the hypothesis that delayed protection is associated with limited infarction and involves altered expression of pro-apoptotic and/or anti-apoptotic proteins. METHODS: Rabbits were treated with phenylephrine or an equivalent volume of vehicle (n = 6 per group). Twenty-four hours after pretreatment, isolated hearts were perfused with a bovine erythrocyte suspension in modified Krebs solution, subjected to 45 minutes of global ischemia (37 C), and reperfused for 120 minutes. Infarct size was determined by triphenyltetrazolium chloride staining. Apoptosis was quantified by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. Left ventricular tissue from separate groups of animals (n = 5 per group), 24 hours after pretreatment with phenylephrine or vehicle but without ischemia and reperfusion, was analyzed by Western blotting for content of the anti-apoptotic protein, bclx, and pro-apoptotic protein, bax. RESULTS: Isolated hearts after phenylephrine pretreatment had increased end-reperfusion developed pressures (56.8 +/- 4.9 vs 36.2 +/- 3.9 mm Hg for vehicle, P =.008) and decreased elevated end-diastolic pressures (26.7 +/- 4.5 vs 42.3 +/- 5.0 mm Hg for vehicle, P =.04). Phenylephrine pretreatment abrogated infarction (9.9 +/- 2.4% vs 42.6 +/- 6.3% for vehicle, P =.002) and reduced the number of apoptotic nuclei (24 +/- 4.8 vs 51 +/- 4.6 for vehicle, P = .038). Analysis by Western blotting showed that the ratio of bclx to bax protein increased in phenylephrine-pretreated hearts (2.65 +/- 0.5 vs 1.0 +/- 0.1 for vehicle, P =.008). CONCLUSION: Delayed myocardial protection to infarction mediated by alpha1-adrenoceptor activation involves an increased bclx/bax ratio, thereby limiting apoptotic cell death.

Adrenergic alpha-Agonists↗
PubMed1999

Acute brain death alters left ventricular myocardial gene expression.

OBJECTIVES: The depressed myocardial function observed in brain dead organ donors has been attributed to massive sympathetic discharge and catecholamine cardiotoxicity. Because elevated catecholamines are associated with altered myocardial gene expression, we investigated whether acute brain death from increased intracranial pressure alters the expression of myocardial gene products important in contractility. METHODS: A balloon expansion model was used to increase intracranial pressure in rabbits (n = 22). At timed intervals after brain death, mean arterial pressure, heart rate, electrocardiograms, histologic myocardial injury, and systemic catecholamines were assessed. Messenger RNA levels encoding myofilaments, adrenergic receptors, sarcoplasmic reticulum proteins, transcription factors, and stress-induced programs were measured with blot hybridization of total left ventricular RNA. RESULTS: Increased intracranial pressure induced an immediate pressor response that temporally coincided with diffuse electrocardiographic ST segment changes. Systemic epinephrine and norepinephrine levels concurrently increased (5- to 8-fold within 1 minute), then fell below baseline within 2 hours, and remained depressed at 4 hours. By 1 hour, histologic injury was evident. Four hours after the induction of increased intracranial pressure, levels of messenger RNA-encoding skeletal and cardiac alpha-actins, egr-1, and heat shock protein 70 were significantly increased. Sham-operated animals did not exhibit these changes. CONCLUSIONS: Select changes in myocardial gene expression occur in response to increased intracranial pressure and implicate ventricular remodeling in the myocardial dysfunction associated with acute brain death.

Actin Cytoskeleton↗
PubMed1999

Surgical treatment of interventional coronary angiographic accidents.

Newer methodologies have increased the incidence of coronary interventions. At the authors' institution, 5,614 coronary interventional procedures (28% of all catheterizations) were performed over a 3-year period, from 1995 to 1997. Eighty-one patients (1.4%) suffered angiographic accidents, including coronary artery dissection, free rupture, tamponade, foreign body embolism, and wire entrapment, and were retrospectively reviewed. All patients were taken for emergency surgery in less than 4 hours. The mean age was 61.2 years, 44 (54%) were men, and 37 (46%) were in cardiogenic shock at the time of surgery. Fifty-seven patients (70%) had intraaortic balloon counterpulsation. The number of previous cardiac interventions ranged from one to four with a mean of 1.9. One to five bypass grafts (mean, 2.2) were performed, and three patients required temporary ventricular assist devices. There were six deaths for a 30-day mortality rate of 7.4%. Thirty-two patients (39.5%) suffered significant morbidity, including cerebrovascular accidents, and renal and respiratory failure. Perioperative myocardial infarctions were diagnosed in 39 (48%) patients. Average length of stay was 12.1 days. One-year survival was satisfactory at 90% (73/81), with 56 survivors (77%) regaining normal everyday activity. Early surgical intervention, rapid revascularization, and temporary mechanical support are keys to low mortality in this high-risk group. Identification of high-risk interventions and significant comorbid conditions, with concomitant surgical consultation, need to be pursued to reduce the high morbidity rate.

Activities of Daily Living↗
PubMed1998

Transcription rates of SERCA and phospholamban genes change in response to chronic stimulation of skeletal muscle.

Chronic low frequency stimulation of predominantly fast-twitch skeletal muscles decrease the levels of SERCA1 (fast-twitch sarco(endo)plasmic reticulum Ca2+-ATPase) mRNA, and increase the levels of SERCA2 (slow-twitch sarco(endo)plasmic reticulum Ca2+-ATPase) and phospholamban mRNAs. To assess the role of transcription in these changes in mRNA levels, nuclei were isolated from chronically stimulated canine latissimus dorsi muscles and transcription rates were estimated by nuclear run-on assays. Decreases in the rates of SERCA1 gene transcription matched the fall in its mRNA level and increases in the rates of SERCA2 and phospholamban gene transcription matched the increases in their mRNAs.

Animals↗
PubMed1998

Decreased expression of tissue inhibitor of metalloproteinase 1 in stunned myocardium.

Ultrastructural studies of stunned myocardium have shown disorganization and loss of extracellular collagen and increased collagenase activity early after ischemia and reperfusion. The interplay between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) regulates the turnover of cardiac extracellular matrix fibrillar collagens. However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known. Here, we determined whether altered expression of MMP-1 and TIMP-1 occurs in globally stunned hearts. An isolated nonworking rabbit heart preparation, perfused with a bovine erythrocyte suspension in modified Krebs solution, was used. Two groups were studied: the stunned group was subjected to 20 min of normothermic global ischemia followed by 120 min of normal reperfusion (n = 8), and the control group underwent 140 min of uninterrupted perfusion (n = 7). The developed pressures at the end of reperfusion for ischemic and control hearts were 67.0 +/- 2.73 and 83.1 +/- 1.52 mm Hg (P < 0. 006) respectively. Ribonuclease protection assays of total left ventricular RNA using riboprobes for MMP-1, TIMP-1, and 18S rRNA were performed. A significant decrease (twofold, P < 0.03) in TIMP-1 gene expression was found in the stunned hearts, while MMP-1 mRNA expression was unchanged. Thus, in early stunning, the decrease in TIMP-1 expression could tip the balance favoring enhanced metalloproteinase activity, promoting collagen turnover, and initiating extracellular matrix remodeling. This may contribute to delayed recovery from myocardial stunning.

Animals↗
PubMed1998

The beta2-agonist salbutamol affects the expression of phospholamban and both isoforms of SERCA in canine skeletal muscle and blocks changes in these induced by neuromuscular stimulation.

Chronic administration of salbutamol induced expression of hybrid fibers in canine skeletal muscles. Fast-twitch fibers expressed SERCA2a (the slow-twitch isoform of sarcoplasmic reticulum Ca2+-ATPase) and slow-twitch fibers expressed SERCA1 (the fast-twitch isoform of the Ca2+-ATPase). The proportion of fibers that became hybrid increased from a small percentage in the control muscles to 30% in the predominantly fast-twitch latissimus dorsi and to 45% in the predominantly slow-twitch vastus intermedius. In contrast to this response by the SERCA genes the phospholamban gene response was muscle specific. The fraction of fibers that expressed phospholamban decreased slightly in the latissimus dorsi while increasing moderately in the vastus intermedius. The effects of chronic neurostimulation of the latissimus dorsi on SERCA1, SERCA2a and phospholamban levels were mostly blocked by salbutamol. While 100% of fibers from neurostimulated muscles expressed phospholamban, only 51% of the fibers from the neurostimulated and salbutamol-treated muscles expressed it. In the neurostimulated muscle, very few muscle fibers expressed SERCA1a while 61% of the fibers that received salbutamol expressed it, albeit as hybrid fibers. The levels of SERCA2a in response to these interventions were just the opposite. In the neurostimulated muscle 37.5% of fibers were hybrid and 62.5% expressed SERCA2a only. With co-administration of neurostimulation and salbutamol, 61.3% of fibers were hybrid and 38.7% expressed SERCA2a only.

Adrenergic alpha-2 Receptor Agonists↗