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Biomedical subjects

M P Anstadt

Publications and source records attributed to M P Anstadt.

At least 19 recordsLinked to original sources
PubMed1996

Chronic hypoxia induces adaptive metabolic changes in neonatal myocardium.

The effect of chronic hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic ischemia to determine high-energy phosphate levels, glycogen stores, and lactate accumulation. Time to peak ischemic myocardial contracture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/gm dry wt, p = 0.001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group. Initial energy charge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia. Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14.7 micromol/gm dry weight, p = 0.02) when compared with the control group. Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of ischemia. Time to peak ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic ischemia. These beneficial effects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis during ischemia.

Animals↗
PubMed1995

The effect of cardiac compression on defibrillation efficacy and the upper limit of vulnerability.

INTRODUCTION: We determined the effects of decreasing the ventricular blood volume and altering cardiac geometry on defibrillation, the upper limit of vulnerability (ULV), and the relationship between them. METHODS AND RESULTS: In six pigs, fibrillation/defibrillation trials were performed with a left ventricular apex patch to a superior vena cava catheter electrode configuration and a biphasic waveform. Thirty trials each were performed on a compressed versus noncompressed (normal) heart. Compression was achieved using direct mechanical ventricular actuation. Dose-response curves were constructed, and the 50% probability points (ED50) were compared for leading edge voltage (LEV), leading edge current (LEI), and total energy (TE). In another 12 pigs, triplicate defibrillation thresholds (DFTs) and ULVs were determined for each heart state. The T wave was scanned with shocks in 10-msec steps for determining the ULV. Compression resulted in decreased ED50s for LEV (delta = 138 +/- 77 V, P < 0.05, mean +/- SD), LEI (delta = 1.57 +/- 0.7 A, P < 0.05), and TE (delta = 4.9 +/- 3.6 J, P < 0.05) compared to normal. In the second study, compression significantly reduced DFT (P < 0.02) and ULV (P < 0.02) for LEV, LEI, and TE compared to normal. The ULV tended to be lower than the DFT for the normal heart state (delta = 23 +/- 46 V LEV: P = NS). However, the ULV was significantly greater than the DFT for the compressed heart state (delta = 19 +/- 25 V LEV; P < 0.03). CONCLUSIONS: Shock delivery during cardiac compression improves defibrillation efficacy. Additionally, cardiac compression decreases both DFT and ULV, which supports the ULV hypothesis of defibrillation. Finally, maintaining the heart's geometric and volumetric state during ULV testing in paced rhythm and DFT testing in ventricular fibrillation moves the ULV higher than the DFT-the position predicted by the ULV hypothesis for defibrillation.

Animals↗
PubMed1994

Pulmonary mucormycosis: results of medical and surgical therapy.

Mucormycosis is an opportunistic fungal infection that commonly begins by invading the respiratory tract. The purpose of the present study was to define the clinical presentation of pulmonary mucormycosis and to evaluate current treatment regimens. Thirty patients treated at our institution and 225 cases reported in the literature were reviewed. For the combined groups, the mean age at presentation was 41 +/- 21 years and associated medical conditions included leukemia or lymphoma (37%), diabetes mellitus (32%), chronic renal failure (18%), history of organ transplantation (7.6%), or a known solid tumor (5.6%). The in-hospital mortality was 65% for patients with isolated pulmonary mucormycosis, 96% for those with disseminated disease, and 80% overall. The mortality in patients treated surgically was 11%, significantly lower than the 68% mortality in those treated medically (p = 0.0004). The most common causes of death were fungal sepsis (42%), respiratory insufficiency (27%), and hemoptysis (13%). Pulmonary mucormycosis has a high mortality; however, antifungal agents appear to improve survival. In addition, surgical resection may provide additional benefit to patients with pulmonary mucormycosis confined to one lung.

Adolescent↗
PubMed1994

Regulation of glucose utilization during the inhibition of fatty acid oxidation in rat myocytes.

The study of the regulation of glucose utilization by inhibition of fatty acid oxidation is greatly enhanced by the availability of specific inhibitors of fatty acid oxidation. This study examines the regulation of cardiac glucose utilization by inhibition of fatty acid oxidation at different sites. The effects of Etomoxir and 4-bromocrotonic acid (4-BCA) on the oxidation of [1-14C]palmitate, [1-14C]-octanoate and [U-14C]glucose were studied in isolated rat myocytes. Fifty percent inhibition of palmitate oxidation was achieved at 8 microM Etomoxir and 40 microM 4-BCA. Octanoate oxidation was inhibited only by 4-BCA. In contrast to their effect on palmitate oxidation, these inhibitors significantly stimulated the oxidation of glucose in a concentration-dependent manner. Moreover, the oxidation of [2-14C]pyruvate was increased two-fold by these compounds. The rate of utilization of [U-14C]-2-deoxyglucose was also stimulated 2-3 times by these inhibitors. These studies suggest that the stimulation of glucose utilization via the inhibition of fatty acid oxidation may be mediated through the stimulation of both glucose transport and the oxidation of pyruvate by the pyruvate dehydrogenase complex.

Animals↗
PubMed1993

Argon beam coagulation compared with cryoablation of ventricular subendocardium.

The Argon Beam Coagulator uses radiofrequency energy to excite argon gas that may be used for ventricular ablation. The effects of power level and number of applications of the Argon Beam Coagulator were compared wtih cryothermia. Ten mongrel dogs underwent cardiac extirpation. The endocardial surfaces of 5 hearts were used for the creation of lesions using the Argon Beam Coagulator at five power levels with either one or two applications. Five hearts were used for endocardial and epicardial lesions using cryothermia (15-mm-diameter probe at -70 degrees C) for 1, 2, 3, or 4 minutes. The Argon Beam Coagulator lesions showed an increase in depth with increasing power levels (2.25 +/- 1.05 mm at 50 W to 6.64 +/- 0.75 mm at 150 W) and number of applications (maximum depth of 6.64 +/- 0.75 mm with one application, 11.2 +/- 1.1 mm with two applications). Cryothermia lesions were similar in depth regardless of duration or site of application (range, 6.1 to 10.2 mm). Both techniques resulted in homogeneous and well-demarcated lesions. These data show that the Argon Beam Coagulator results in discrete endocardial lesions, which may be created quickly and reproducibly. This may be a useful alternative for the operative ablation of endocardial scar in the treatment of ventricular tachycardia.

Animals↗
PubMed1993

Pulsatile versus nonpulsatile reperfusion improves cerebral blood flow after cardiac arrest.

Cardiopulmonary bypass using nonpulsatile flow (NF) is currently advocated for treating refractory cardiac arrest. Although the heart can be revived using cardiopulmonary bypass support, the brain must recover if such therapy is to be considered successful. Previous studies have demonstrated that pulsatile flow (PF) reperfusion can improve neurologic outcome compared with NF reperfusion after cardiac arrest. The purpose of this study was to assess cerebral perfusion and oxygen consumption during either PF or NF reperfusion after cardiac arrest. Dogs (n = 22) underwent a 15-minute cardiac arrest followed by 1 hour of either PF or NF reperfusion. Microsphere techniques were used to assess cerebral perfusion and oxygen consumption at 3, 15, and 60 minutes of reperfusion. Mean arteriovenous gradients and total brain flows were similar in both groups. However, cerebral oxygen consumption was significantly improved at 3 minutes of reperfusion with PF versus NF (1.8 +/- 0.3 versus 0.9 +/- 0.3 mL O2.dL-1.min-1, respectively; p < 0.05). These results were coincident with improved gray-to-white flow ratios at 3 minutes of PF versus NF reperfusion (5.2 +/- 1.0 versus 2.0 +/- 0.3, respectively; p < 0.05). There were no statistically significant differences in brain perfusion variables by 15 minutes of reperfusion. However, a relative hyperemia was exhibited at 15 minutes of NF versus PF reperfusion, which suggests nutrient flow was insufficient during early NF versus PF reperfusion. In conclusion, PF reperfusion can better restore cerebral blood flow and oxygen consumption than can NF reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Stimulation of myocyte insulin-responsive glucose transporters by the inhibition of fatty acid oxidation.

The effects of the fatty acid inhibitor 4-bromocrotonic acid (4-BCA) on glucose utilization was studied in isolated rat myocytes. In contrast to its potent inhibition of [1-14C]palmitate oxidation, 4-BCA strongly stimulated the oxidation of [1-14C]glucose and [2-14C]-pyruvate in a concentration-dependent manner. At a concentration of 300 microM, 4-BCA increased glucose oxidation threefold and that of pyruvate oxidation twofold. The rate of transport of [U-14C]-2-deoxyglucose was significantly stimulated by 4-BCA. The transport of 2-deoxyglucose was increased sevenfold with 200 microM 4-BCA, whereas insulin (10 microU)/ml enhanced 2-deoxyglucose transport twofold. The addition of insulin to myocytes preincubated with 4-BCA did not further increase glucose transport. Cytochalasin B and anti-GLUT 4 antibody decreased the 4-BCA-induced stimulation of glucose transport. These results suggest that the stimulation of 2-deoxy-glucose transport by 4-BCA occurs through an increase in the activity of insulin-responsive glucose transporters, GLUT 4, in the sarcolemmal membrane.

Animals↗
PubMed1992

Current morbidity, mortality, and survival after bronchoplastic procedures for malignancy.

The number of patients reported to have undergone bronchoplastic procedures has increased nearly fourfold in the past decade. These techniques represent excellent surgical therapy for patients with benign endobronchial lesions, traumatic airway disruptions, or tumors of low-grade malignant potential, and for select patients with surgically resectable lung cancer. Eighty-nine percent of bronchoplastic procedures are performed for malignancy. We reviewed 1,915 bronchoplastic procedures for carcinoma reported over the past 12 years to determine the incidence of complications and survival. Complications included local recurrence (10.3%), 30-day mortality (7.5%), pneumonia (6.7%), atelectasis (5.4%), benign stricture or stenosis (5.0%), bronchopleural fistulas (3.5%), empyema (2.8%), bronchovascular fistulas (2.6%), and pulmonary embolism (1.9%). Results were further stratified into sleeve lobectomy and sleeve pneumonectomy groups. Five-year survivals for stage I, II, and III carcinoma were 63%, 37%, and 21%, respectively. Sleeve lobectomy for carcinoma extends surgical therapy to select patients with complication rates comparable to pneumonectomy and long-term survival similar to that for conventional resections.

Bronchi↗
PubMed1991

First successful bridge to cardiac transplantation using direct mechanical ventricular actuation.

Currently available ventricular assist devices are technically difficult to implant, require continuous anticoagulation, and are associated with hemorrhagic and thromboembolic complications. Direct mechanical ventricular actuation is a biventricular assist device that can be applied in 3 to 5 minutes through a left anterior thoracotomy and has no direct blood contact or need for anticoagulation. The present study was designed to determine the effects of direct mechanical ventricular actuation in total biventricular circulatory support. Cardiogenic shock refractory to standard therapy developed in 2 patients awaiting cardiac transplantation. Direct mechanical ventricular actuation was applied and provided immediate hemodynamic stabilization in both. All inotropic agents and intraaortic balloon support were then discontinued. Fifty-six hours of circulatory support bridged the first patient to successful cardiac transplantation without complication. The patient is alive and well more than 1 year later without incident of infection or rejection. The second patient suffered cardiac arrest and required closed chest cardiopulmonary resuscitation before device application. After 45 hours of support, it was determined that irreversible neurologic injury had occurred and direct mechanical ventricular actuation was discontinued. Neither patient's native heart exhibited any histologic evidence of device-related trauma. Direct mechanical ventricular actuation has undergone limited clinical investigation since its original description 25 years ago, but in these initial trials, the device has proved effective. The concept of mechanically actuating the ventricles appears to be a valuable, yet under-utilized method of total circulatory support.

Blood Pressure↗
PubMed1991

Direct mechanical ventricular actuation: a review.

Direct mechanical ventricular actuation (DMVA) is a non-blood contacting method of circulatory support that can be rapidly instituted for resuscitation. DMVA is superior to conventional methods (open and closed-chest cardiac massage) in providing reliable cardiovascular stabilization for resuscitation following cardiac arrest. Furthermore, DMVA has important advantages including rapid application, technical simplicity, and avoidance of blood contact compared to other resuscitation devices (cardiopulmonary bypass and blood pumps). This review summarizes laboratory and clinical applications of DMVA.

Animals↗
PubMed1991

Pulsatile reperfusion after cardiac arrest improves neurologic outcome.

Cardiopulmonary bypass (CPB) using nonpulsatile flow (NPF) is advocated for refractory cardiac arrest. This study examined cerebral outcome after resuscitation with pulsatile flow (PF) versus NPF. Dogs arrested for 12.5 minute were reperfused with NPF (n = 11) using roller pump CPB or PF (n = 11) using mechanical biventricular cardiac massage. Pump flows were similar between groups; however early arterial pressures were greater during PF versus NPF, *p less than 0.05. Circulatory support was weaned at 60 minutes' reperfusion. Neurologic recovery of survivors (n = 16) was significantly better after PF versus NPF, *p = 0.01. The presence of brain lesions on magnetic resonance images did not significantly differ between groups at 7 days. Brain then were removed and regions examined for ischemic changes. Loss of CA1 pyramidal neurons was more severe after NPF versus PF, +p = 0.009. Ischemic changes were more frequent after NPF in the caudate nucleus (+p = 0.009) and watershed regions of the cerebral cortex (+p = 0.062), compared with PF. These results demonstrate that PF improves cerebral resuscitation when treating cardiac arrest with mechanical circulatory support (* = MANOVA with repeated measures, + = categorical data analysis.

Analysis of Variance↗
PubMed1991

Direct mechanical ventricular actuation for cardiac arrest in humans. A clinical feasibility trial.

Direct mechanical ventricular actuation (DMVA) is a non-blood-contacting method of biventricular cardiac massage which may be applied expediently for total circulatory support. The purpose of this study was to assess the feasibility of DMVA application for patients suffering refractory cardiac arrest. Following informed consent, DMVA was applied in 22 patients. Vascular access for hemodynamic monitoring was possible in only 12 patients, whose outcomes serve as the basis for this report. The mean age of the patients was 48.2 +/- 4.2 years (seven men; five women). The average time from witnessed cardiac arrest to DMVA application was 81 +/- 9 minutes. Application took less than two minutes from the time of skin incision and resulted in immediate hemodynamic improvement. Systolic and diastolic blood pressures averaged 78 +/- 4 and 41 +/- 4 mm Hg, respectively, with a mean cardiac output of 3.14 +/- 0.18 L/min during a mean of 228 +/- 84 minutes of circulatory support (range, 25 minutes to 18 hours). In selected cases the device was temporarily removed for 2 to 3 minutes and open-chest cardiac massage (OCCM) performed at similar compression rates. DMVA increased arterial pressures 65 percent and cardiac output 190 percent compared to OCCM. Initial arterial pH (7.12 +/- 0.04) improved by the time the device was removed (7.24 +/- 0.05). Serum lactate levels decreased from 18.0 +/- 2.3 mumol/L to 14.9 +/- 2.9 mumol/L. Four patients were successfully defibrillated: two had inadequate cardiac function and died within 1 h, and two were successfully resuscitated, but later died from cardiac failure and respiratory insufficiency. Another patient regained normal neurologic function during DMVA and was successfully bridged to cardiopulmonary bypass for emergent coronary artery bypass grafting, but died later from myocardial infarction. There were only two complications: (1) a cardiac laceration during pericardiotomy (1/22 patients); and (2) a ventricular rupture during OCCM (1/22). No complication resulted from the device. We found DMVA to be a feasible method for acute cardiovascular stabilization in victims suffering refractory cardiac arrest. Human clinical trials employing earlier DMVA application are required to determine its resuscitative potential.

Blood Pressure↗
PubMed1990

Surgical treatment of automatic atrial tachycardias.

From 1979 to 1989, 18 patients were seen in the Electrophysiology Service, Duke University Medical Center, with automatic atrial tachycardia. There were 8 male and 10 female patients with a mean age of 28.1 +/- 2.9 years. Electrophysiological mapping localized automatic foci to right atrial sites (14 patients) and left atrial sites (4 patients). Depending on origin of the focus, patients were further diagnosed as having either chronic ectopic atrial tachycardia or inappropriate sinus tachycardia. Of the 15 patients with chronic ectopic atrial tachycardia, 6 responded to medical treatment; in 9, the tachycardia was not adequately controlled. Six of them were referred for surgical intervention. All 3 patients with inappropriate sinus tachycardia underwent operative therapy. In the surgical group of patients with chronic ectopic atrial tachycardia, all 6 had a tachycardia-induced cardiomyopathy with ejection fractions ranging from 14% to 27% (mean ejection fraction, 21% +/- 2.7%). Surgical techniques used (alone or in combination) included an isolation procedure in 1 patient, cryoablation in 4 patients, and excision of atrial appendages or portions of atrial free walls in 7. Normal sinus rhythm developed in all surgical patients except 1 patient who had intractable congestive heart failure preoperatively and died of this condition and stroke. The overall success rates for medical and surgical therapy were 33.3% and 88.9%, respectively (p less than 0.01). Long-term follow-up was possible for 7 (87.5%) of 8 patients 3 to 7 years after operation. All patients with chronic ectopic atrial tachycardia were cured, but only 1 of 3 patients with inappropriate sinus tachycardia was in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Mechanical myocardial actuation during ventricular fibrillation improves tolerance to ischemia compared with cardiopulmonary bypass.

Direct mechanical ventricular actuation (DMVA) is a unique non-blood-contacting biventricular assist device that provides circulatory support during ventricular fibrillation without demonstrating adverse effects on the myocardium. The purpose of this study was to assess the preservation of myocardial energy stores and myocardial responses to ischemia after circulatory support during ventricular fibrillation with direct mechanical ventricular actuation versus cardiopulmonary bypass. Twenty adult mongrel dogs were randomized to receive circulatory support with either cardiopulmonary bypass or direct mechanical ventricular actuation. After 4 hours of ventricular fibrillation, hearts were defibrillated and left ventricular transmural biopsies were obtained. Hearts were then excised and subjected to 90 minutes of normothermic total ischemia. Serial biopsies were obtained at 15-minute intervals to determine regional depletion of high energy phosphates. The time-to-peak ischemic contracture was recorded by using needle-tipped Millar catheters placed in the left ventricular endocardium, epicardium, septum, and right ventricle. Time-to-peak ischemic contracture of the endocardium (62.6 +/- 1.4 vs. 58.8 +/- 1.0 minutes, p less than 0.05) and septum (61.1 +/- 6.9 vs. 46.9 +/- 6.2 minutes, p less than 0.004) were significantly prolonged after direct mechanical ventricular actuation versus cardiopulmonary bypass, respectively. Similar trends were noted in the epicardium and right ventricular regions; however, these differences were not statistically significant. Left ventricular adenosine triphosphate (ATP) levels were better preserved after direct mechanical ventricular actuation (22 +/- 1.5 mumols/g dry wt) compared with cardiopulmonary bypass (17 +/- 1.9 mumols/g dry wt). The depletion of left ventricular endocardium ATP during normothermic ischemia was significantly delayed after direct mechanical ventricular actuation compared with cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Optimal temperature for preservation of donor myocardium.

The ideal method for the preservation of donor hearts for transplantation is unclear. To assess the optimal temperature for donor myocardium preservation, the recovery of isolated canine hearts (n = 20) exposed to 4 hours of either standard ice-chest hypothermia (0-4 degrees C) or constant moderate hypothermia (12 degrees C) were compared. Functional and metabolic data were acquired before hypothermia and every 30 minutes during 3 hours of reperfusion with oxygenated blood. Mean end-systolic pressure-volume slopes were 2.11 +/- 0.06 and 2.09 +/- 0.06 mm Hg/ml for ice-chest hypothermia and constant moderate hypothermia, respectively (p = NS), which were unchanged from control. All y intercepts during reperfusion were decreased compared with control (p = 0.002) without any differences between groups. End-diastolic pressures were greater than control throughout the reperfusion period for both groups (p = 0.02), but there was a difference in change of end-diastolic pressures with time between groups (p = 0.04). Dry/wet ratios were similar after preservation and reperfusion in both groups. ATP recovered to control levels during reperfusion for both groups although energy charge ratios were greater for hearts exposed to constant moderate hypothermia (p = 0.007). These data indicate that intracellular energy stores are well maintained by preservation using either technique. Changes in function appear to be related to altered compliance irrespective of preservation temperature. These data suggest that a wide range of temperatures may be acceptable for donor heart preservation.

Animals↗
PubMed1990

Mechanical cardiac actuation achieves hemodynamics similar to cardiopulmonary bypass.

The disadvantages of blood/interface interactions and difficult installation are common to current circulatory support devices. Direct mechanical ventricular actuation (DMVA) is a method of biventricular cardiac massage that avoids contact of blood with various surfaces. The purpose of this study was to compare hemodynamic responses and organ perfusion between DMVA and cardiopulmonary bypass (CPB). Twenty adult mixed-breed dogs randomized for DMVA or CPB were anesthetized with alpha-chloralose. During 4 hours of ventricular fibrillation, animals received either DMVA or CPB with aortic arch perfusion (90 to 120 ml/kg/min), bicaval venous return, and full left ventricle venting. Hemodynamics and organ perfusion were assessed by multivariant analysis of variance with repeated measures. Blood flow was similar to normal sinus rhythm (control) with either method; however, average CPB flows (control, 110%) were increased significantly over DMVA flows (control, 75%) (p = 0.016). The resulting mean arterial pressures were significantly greater during DMVA (control, 66%) compared to CPB (control, 49%) (p = 0.0011). Radiolabeled microspheres were the measure of organ perfusion during sinus rhythm and at 2 and 4 hours of circulatory support. Myocardial blood flow was equal to control in all regions during DMVA; CPB resulted in increased flows to the left ventricular epicardium, septum, and right ventricle. DMVA generated significantly greater flows to the renal cortex. All other organs demonstrated similar perfusion with either method. However, CPB displayed declining cerebral flows at 4 hours compared to DMVA (42% vs 55% control, respectively). Overall, DMVA provided hemodynamic stability equal to that of CPB. Rapid application and avoidance of blood/surface contact make DMVA a favorable method of temporary circulatory support.

Animals↗