Biomedical subjects

J L Zellner

Publications and source records attributed to J L Zellner.

At least 37 records · Page 2Linked to original sources

PubMed1998

Angiotensin converting enzyme inhibition, AT1 receptor inhibition, and combination therapy with pacing induced heart failure: effects on left ventricular performance and regional blood flow patterns.

BACKGROUND: AT1 receptor activation has been demonstrated to cause increased vascular resistance properties which may be of particular importance in the setting of congestive heart failure (CHF). The overall goal of this study was to examine the effects of ACE inhibition (ACEI) alone, AT1 receptor blockade alone and combined ACEI and AT1 receptor blockade on LV pump function, systemic hemodynamics and regional blood flow patterns in the normal state and with the development of pacing induced CHF, both at rest and with treadmill induced exercise. METHODS AND RESULTS: Pigs (25 kg) were instrumented in order to measure cardiac output (CO), systemic (SVR) and pulmonary vascular (PVR) resistance, neurohormonal system activity, and myocardial blood flow distribution in the conscious state and assigned to one of 4 groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n = 7); (2) ACEI (benazeprilat, 3.75 mg/day) and pacing (n = 7); (3) AT1 receptor blockade (valsartan, 60 mg/day) and rapid pacing (n = 7); and (4) ACEI and AT1 receptor blockade (benazeprilat/valsartan, 1/60 mg/day, respectively) and pacing (n = 7). Measurements were obtained at rest and with treadmill exercise (15 degrees, 3 miles/h; 10 min) in the normal control state and after the completion of the treatment protocols. With rapid pacing, CO was reduced at rest and with exercise compared to controls. ACEI or AT1 blockade normalized CO at rest, but remained lower than control values with exercise. Combination therapy normalized CO both at rest and with exercise. Resting SVR in the CHF group was higher than controls and SVR fell to a similar degree with exercise; all treatment groups reduced resting SVR. With exercise, SVR was reduced from rapid pacing values in the ACEI and combination therapy groups. PVR increased by over 4-fold in the rapid pacing group both at rest and with exercise, and was reduced in all treatment groups. In the combination therapy group, PVR was similar to control values with exercise. Plasma catecholamines and endothelin levels were increased by over 3-fold with chronic rapid pacing, and were reduced in all treatment groups. In the combination therapy group, the relative increase in catecholamines and endothelin with exercise were significantly blunted when compared to rapid pacing only values. LV myocardial blood flow at rest was reduced in the rapid pacing only and monotherapy groups, but was normalized with combination therapy. CONCLUSION: These findings suggest that with developing CHF, combined ACE inhibition and AT1 receptor blockade improved vascular resistive properties and regional blood flow distribution to a greater degree than that of either treatment alone. Thus, combined ACEI and AT1 receptor blockade may provide unique benefits in the setting of CHF.

Angiotensin I↗

PubMed1998

Isolated left ventricular myocyte contractility in patients undergoing cardiac operations.

BACKGROUND: Because of methods required for obtaining isolated left ventricular myocytes, evaluation of the contractile function of isolated left ventricular myocytes in normal human patients has been limited. Accordingly, the goal of the present study was to develop a means to isolate human left ventricular myocytes from small myocardial biopsy specimens collected from patients undergoing elective coronary artery bypass operations and to characterize indices of myocyte contractile performance. METHODS: Myocardial biopsy specimens were obtained from the anterior left ventricular free wall of 22 patients undergoing coronary artery bypass operations. Myocytes were isolated from these myocardial samples by means of a stepwise enzymatic digestion method and micro-trituration techniques. Isolated left ventricular myocyte contractile function was assessed by computer-assisted high-speed videomicroscopy under basal conditions and in response to beta-adrenergic receptor stimulation with isoproterenol. RESULTS: A total of 804 viable left ventricular myocytes were successfully examined from all of the myocardial biopsy specimens with an average of 37+/-4 myocytes per patient. All myocytes contracted homogeneously at a field stimulation of 1 Hz with an average percent shortening of 3.7%+/-0.1% and shortening velocity of 51.3+/-1.3 microm/s. After beta-adrenergic receptor stimulation with isoproterenol, percent shortening and shortening velocity increased 149% and 118% above baseline, respectively (P < .05). CONCLUSION: The unique results of the present study demonstrated that a high yield of myocytes could be obtained from human left ventricular biopsy specimens taken during cardiac operations. These myocytes exhibited stable contractile performance and maintained the capacity to respond to an inotropic stimulus. The methods described herein provide a basis by which future studies could investigate intrinsic and extrinsic influences on left ventricular myocyte contractility in human beings.

Adrenergic beta-Agonists↗

PubMed1997

Pneumoperitoneum to treat air leaks and spaces after a lung volume reduction operation.

Lung volume reduction surgery is an option for the management of end-stage emphysema. The most frequent surgical complication of lung volume reduction is prolonged air leaks. We describe a patient undergoing a lung volume reduction operation complicated by persistent bilateral air spaces with large air leaks. Treatment with recurrent pneumoperitoneum via a peritoneal dialysis catheter along with chemical sclerosis successfully resolved both problems.

Air↗

PubMed1997

Reducing cardiac surgical trauma: the minimally invasive direct coronary artery bypass.

BACKGROUND: The concept of minimal surgical trauma is revolutionizing many surgical subspecialties, including cardiac surgery. Coronary artery revascularization can now be accomplished either thoracoscopically or through a small thoracotomy, sternotomy, or epigastric incision, with or without cardiopulmonary bypass (CPB). METHODS: The current literature was reviewed with regard to patient selection criteria for coronary artery bypass grafting (CABG) without CPB, indications for minimally invasive direct coronary artery bypass (MIDCAB), surgical and anesthetic technique, and outcome. RESULTS: The MIDCAB is largely used in cases of single or double vessel disease. The procedure is done either thoracoscopically or under direct vision through a small incision rather than standard sternotomy. In non-CPB cases, the heart is pharmacologically manipulated to create a quiet operative field. Patients may be extubated and become ambulatory shortly after surgery and be discharged within a few days. CONCLUSIONS: The MIDCAB avoids median sternotomy and, in many cases, CPB. MIDCAB may prove to play a prominent role in management of coronary artery disease in the future.

Anesthesia↗

PubMed1996

Contributory mechanisms for the beneficial effects of myocyte preconditioning during cardioplegic arrest.

BACKGROUND: Preconditioning protects the myocardium from ischemia and may be a potent means of endogenous cardioprotection during cardioplegic arrest and rewarming. However, fundamental mechanisms that potentially contribute to the beneficial effects of preconditioning during cardioplegic arrest and rewarming remain unclear. Accordingly, the overall goal of the present study was to examine the potential mechanisms by which preconditioning protects myocyte contractile function during simulated cardioplegic arrest and rewarming. METHODS AND RESULTS: Left ventricular isolated porcine myocyte contractile function was examined with the use of videomicroscopy under three conditions: (1) normothermia, maintained in cell medium (37 degrees C) for 2 hours; (2) simulated cardioplegic arrest and rewarming, incubated in crystalloid cardioplegic solution (24 mEq/L K+, 4 degrees C) for 2 hours followed by normothermic reperfusion; and (3) preconditioning/cardioplegic arrest and rewarming, hypoxia (20 minutes) and reoxygenation (20 minutes) followed by simulated cardioplegic arrest and rewarming. Cardioplegic arrest and rewarming caused a decline in steady-state myocyte shortening velocity compared with normothermic controls (22.0 +/- 1.6 versus 57.2 +/- 2.6 microns/s, respectively, P < .05), which was significantly improved with preconditioning (36.1 1.7 microns/s, P < .05). In the next series of experiments, the influence of nonmyocyte cell populations with respect to preconditioning and cardioplegic arrest was examined. Endothelial or smooth muscle cell cultures were subjected to a period of hypoxia (20 minutes) and reoxygenation (20 minutes) and the eluent incubated with naive myocytes, which were then subjected to simulated cardioplegic arrest and rewarming. Pretreatment with the eluent from endothelial cultures followed by cardioplegic arrest and rewarming improved myocyte function compared with cardioplegia-alone values (31.7 +/- 2.2 versus 24.7 +/- 1.6 microns/s, respectively, P < .05), whereas smooth muscle culture eluent pretreatment resulted in no change (23.7 +/- 4.0 microns/s, P = .81). Molecular mechanisms for the protective effects of preconditioning on myocyte contractile processes with cardioplegic arrest and rewarming were examined in a final series of experiments. Adenosine-mediated pathways or ATP-sensitive potassium channels were activated by augmenting cardioplegic solutions with adenosine (200 mumol/L) or the potassium channel opener aprikalim (100 mumol/L), respectively. Both adenosine and aprikalim augmentation significantly improved myocyte function compared with cardioplegia-alone values (53.5 +/- 1.7, 57.6 +/- 2.0 versus 25.7 +/- 1.4 microns/s, respectively, P < .05). CONCLUSIONS: The unique findings from the present study demonstrated that preconditioning provides protective effects on myocyte contractile processes independent of nonmyocyte cell populations and that these effects are mediated in part through the activation of adenosine pathways or ATP-sensitive potassium channels. Thus, preconditioning adjuvant to cardioplegia may provide a novel means of protecting myocardial function after cardioplegic arrest and rewarming.

Adenosine↗

PubMed1996

Cellular and extracellular remodeling with the development and recovery from tachycardia-induced cardiomyopathy: changes in fibrillar collagen, myocyte adhesion capacity and proteoglycans.

The myocardial extracellular matrix (ECM) is composed of three important constituents: (1) fibrillar collagen, (2) a basement membrane, and (3) proteoglycans. Structural or compositional changes in these ECM components may affect left ventricular (LV) function as well as influence overall LV geometry. Accordingly, this study examined the relationship between changes in these ECM components to changes in LV function and geometry which develop with the progression and regression from supraventricular tachycardia-induced cardiomyopathy (SVT). LV function and specific components of the ECM were studied in pigs with SVT cardiomyopathy (SVT:atrially paced 240 bpm, 3 weeks; n = 7), or after a 4-week recovery from SVT cardiomyopathy (post-SVT; n = 6), and in controls (n = 7). LV fractional shortening fell by 60% and end-diastolic dimension increased by 47% with SVT compared to controls. While LV fractional shortening normalized with post-SVT, end-diastolic dimension remained 40% higher than controls. Collagen concentration fell by 22% and salt extractable collagen, which reflects collagen cross-linking, increased by 41% with SVT compared to controls. Collagen concentration increased by 20%, collagen extraction normalized, and levels of collagen type III mRNA increased by 42% with post-SVT. Isolated myocyte adhesion capacity to basement membrane substrates laminin, fibronectin, and collagen type IV were examined. SVT resulted in over a 50% reduction in myocyte adhesion for all of the basement membrane components compared to controls. A normalization in isolated myocyte adhesion capacity was observed in post-SVT. The relative content and distribution of the ECM proteoglycan chondroitin sulfate was examined using immunohistochemistry. With SVT, the density of this proteoglycan increased around individual myocytes. With post-SVT, the relative distribution of chondroitin sulfate returned to control levels. Thus, SVT cardiomyopathy was associated with reduced collagen concentration and cross-linking, diminished myocyte basement membrane adhesion capacity, and increased proteoglycans. Recovery from SVT cardiomyopathy resulted in increased collagen concentration, and a normalization of myocyte adhesion capacity and proteoglycan distribution. These results suggest that changes within the ECM are a dynamic process and accompany the LV systolic and diastolic function as well as ventricular and myocyte remodeling during the progression and regression from cardiomyopathic disease.

Analysis of Variance↗

PubMed1996

Beneficial effects of myocyte preconditioning on contractile processes after cardioplegic arrest.

BACKGROUND: Myocardial precondition, which can be achieved through short intervals of ischemia or hypoxia followed by reperfusion, protects the myocardium with subsequent prolonged periods of ischemia. Accordingly, the present study tested the hypothesis that hypoxic preconditioning before cardioplegic arrest would have direct and beneficial effects on myocyte contractile processes with reperfusion. METHODS: Left ventricular porcine myocytes (n = 335) were randomly assigned to one of three treatments: normothermia, maintained in cell media (37 degrees C, 2 hours); cardioplegia, hyperkalemic arrest (24 mEq K+, 4 degrees C, 2 hours) followed by normothermic reperfusion; preconditioning, hypoxia (20 minutes) and reperfusion (20 minutes), and then followed by cardioplegic arrest and rewarming. Myocyte velocity of shortening was measured using computer-assisted videomicroscopy at baseline and with beta-adrenergic receptor stimulation with isoproterenol (25 nmol/L). RESULTS: In the cardioplegia group, myocyte function was reduced at baseline (22 +/- 1 versus 57 +/- 2 microns/s) and with beta-adrenergic receptor stimulation (81 +/- 5 versus 156 +/- 7 microns/s) compared to normothermic controls (p < 0.05). Preconditioning improved myocyte function at baseline (38 +/- 2 microns/s) and with beta-adrenergic receptor stimulation (130 +/- 6 microns/s) compared to the cardioplegic alone group (p < 0.05). CONCLUSIONS: The important findings from this study are twofold. First, preconditioning can be induced directly at the level of the myocyte, independent of nonmyocyte populations and extracellular influences. Second, myocyte preconditioning provides protective effects on myocyte function and beta-adrenergic responsiveness after cardioplegic arrest and rewarming. These findings suggest that preconditioning may provide a novel approach in protecting myocyte contractile processes during cardioplegic arrest.

Adaptation, Physiological↗

PubMed1993

Arterial hemorrhage complicating pancreatic pseudocysts: role of angiography.

Major arterial hemorrhage associated with pancreatic pseudocysts represents a formidable complication with high mortality rates. This study was undertaken to analyze presentation and outcome and to assess the role of angiography in diagnosis and management of this complication. A retrospective review of 180 patients referred for surgical management of pancreatic pseudocysts from 1964 to 1991 identified 13 patients (7.2%) with arterial hemorrhage. Eight patients presented with intracystic hemorrhage, 4 with upper gastrointestinal bleeding, and 1 with intra-abdominal bleeding. Six patients had gastroduodenal artery bleeding, 4 splenic, and 1 each left gastric, right colic, and left gastroepiploic. The site of bleeding was identified with selective visceral angiography in 9 patients; evidence of pseudocyst bleeding was seen in 5 of 7 patients who had contrast-enhanced computerized tomography (CT) scans. Angiographic embolization for control of hemorrhage was used in 6 patients and operative control in 7. Over the past decade, bleeding has been controlled with angiographic embolization in all patients except 1 with massive bleeding due to splenic artery erosion. Average blood loss was less in patients treated with angiographic embolization (6.8 vs 17.5 units, packed red cells, P < .05, Wilcoxon rank sum test). The sole mortality was a patient with cirrhosis treated in 1969. Clinical presentation of pseudocyst bleeding is variable; the underlying cause is usually related to chronic pancreatitis due to alcohol abuse. The dynamic contrast-enhanced CT scan is valuable in demonstrating evidence of pseudocyst bleeding. Accurate diagnosis with dynamic CT scan and angiography and control of bleeding with angiographic embolization has improved the outcome in patients with this complication.

Adolescent↗

PubMed1991

Right ventricular pump dysfunction with acute experimental septic shock.

Right ventricular (RV) function has been poorly characterized at the onset of acute bacterial septic shock. Using a volumetric thermodilution catheter, previously validated in our laboratory, we serially measured RV function in a porcine model of acute septic shock. Six pigs (21.3 +/- 0.9 kg) were instrumented and Pseudomonas aeruginosa (3.4 x 10(8) cfu/ml, 0.3 ml/20 kg/min) was infused. RV ejection fraction, RV volumes, cardiac output, arterial pressure, central venous pressure, and pulmonary arterial pressure were measured at baseline and at 30, 60, 120, and 240 min after starting the bacterial infusion. RV ejection fraction and stroke volume were decreased at 30 min compared to baseline (21 +/- 5 vs 43 +/- 5% and 14 +/- 3 vs 23 +/- 3 ml, respectively; P less than 0.05) and remained depressed throughout the experiment. Mean arterial pressure was significantly reduced at 60, 120, and 240 min compared to baseline (P less than 0.05). There was a significant increase in pulmonary vascular resistance (1771 +/- 493 vs 301 +/- 99 dyn-sec-cm-5 at 30 min; P less than 0.05) and RV stroke work (5.7 +/- 1.1 vs 2.3 +/- 0.3 gm-m/beat at 30 min; P less than 0.05) while no significant change in RV end-diastolic volume or central venous pressure was observed. Thus, a decrease in RV pump performance was associated with an increase in afterload and no change in preload. These results suggest that severe RV pump dysfunction occurs early in acute septic shock. This was manifested by significant reductions in RV ejection fraction and increased in stroke work.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Placement considerations for measuring thermodilution right ventricular ejection fractions.

BACKGROUND AND METHODS: Clinical examination of right ventricular (RV) performance has been hampered by the inability to measure easily RV volumes and ejection fraction. This study was performed to examine the effects of catheter position on thermodilution RVEF measurements. Six pigs (80 to 100 kg) were instrumented with an RV thermodilution catheter in the pulmonary artery, an injectate catheter in the right atrium, an atrial pacing electrode, and a systemic arterial catheter. RVEF measurements were determined using thermodilution in two ways: a) with incremental increases in pulmonary valve to thermistor distance; and b) with incremental increases in injectate port to tricuspid valve distance. These measurements were obtained at a paced rate of 102 +/- 2 beats/min and then repeated with pacing-induced tachycardia (140 beats/min). RESULTS: There was no significant difference in thermodilution RVEF measurements with the thermistor positioned 0 to 10 cm from the pulmonary valve at either heart rate. A significant reduction in RVEF occurred with the injection port located 5 to 7 cm proximal to the tricuspid valve, with this decrease becoming more pronounced during tachycardia. CONCLUSIONS: These results demonstrate that RVEF measurements can be reliably obtained using thermodilution. In these large hearts, thermodilution RVEF measurements appear to be independent of thermistor position within the pulmonary artery. However, large distances from injectate port to tricuspid valve reduced RVEF measurements.

Animals↗

PubMed1991

Tachycardia-induced cardiomyopathy: effects on blood flow and capillary structure.

Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy. A potential factor contributing to the development of SVT-induced cardiomyopathy is abnormal myocardial blood flow (MBF). The purpose of this study was to relate changes in left ventricular (LV) function, MBF, and capillary structure with the development of SVT-induced cardiomyopathy. LV function and MBF were measured in two groups of conscious pigs: sham control (CON; n = 8) and after 3 wk of atrial pacing (SVT; 240 beats/min; n = 8) using echocardiography-catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) during rapid atrial pacing (240 beats/min), and 3) during adenosine infusion (1.5 microM.kg-1.min-1) without pacing. LV capillary density, diameter, wall thickness, and capillary-myocyte distance were measured in four additional pigs from each group. LV fractional shortening was lower, and left atrial pressure was significantly higher in the SVT group compared with CON at rest, during pacing, and with adenosine (P less than 0.05). In the CON group, average LV-MBF at rest was 2.0 +/- 0.2 ml.min-1.g-1, increased with pacing to 3.0 +/- 0.2 ml.min-1.g-1 (P less than 0.05), and increased further with adenosine to 4.1 +/- 0.3 ml.min-1.g-1 (P less than 0.05). In all states, SVT LV-MBF was significantly reduced vs. CON (P less than 0.05); SVT LV-MBF was 0.8 +/- 0.2 ml.min-1.g-1 at rest, increased to 1.3 +/- 0.3 ml.min-1.g-1 with rapid pacing (P less than 0.05), and remained unchanged during adenosine (1.3 +/- 0.4 ml.min-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1991

Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia.

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dYsfunction and dilatation. Termination of SVT appears to improve symptoms of congestive heart failure. However, the structural events that occur during development and regression of SVT-induced cardiomyopathy are unknown. Accordingly, LV function (simultaneous echocardiogram-catheterization) and collagen content and distribution were measured in pigs (23-25 kg) assigned to three groups: 1) rapid atrial pacing (240 beats/min) for 3 wk (SVT, n = 10); 2) SVT for 3 wk, followed by deactivation of the pacemaker and a 4-wk recovery period (PST, n = 9); and 3) sham-operated controls (CON, n = 10). LV fractional shortening was 30 +/- 2% in CON, fell to 13 +/- 2% with SVT (P less than 0.05), and returned to CON values with PST (31 +/- 2%). SVT resulted in significantly increased LV end-diastolic dimension compared with CON (4.9 +/- 0.3 vs. 3.5 +/- 0.2 cm, P less than 0.05) and no change in LV wt/body wt (2.7 +/- 0.2 vs. 2.6 +/- 0.2 g/kg, P = 0.85). Termination of SVT (PST) resulted in development of hypertrophy, LV mass increased to 3.50 +/- 0.3 g/kg (P less than 0.05 vs. CON). With the use of pressure-dimension-thickness relations during diastole, the regional chamber stiffness constant (Kc) was computed. Kc was unchanged by SVT compared with CON (5.3 +/- 1.4 vs. 3.7 +/- 0.5, P greater than 0.35) but increased with PST (7.4 +/- 0.6, P less than 0.05). LV hydroxyproline content significantly fell with SVT compared with CON (2.24 +/- 0.58 vs. 2.68 +/- 0.45 mg/g dry wt, P less than 0.05, respectively) and significantly increased with PST (3.68 +/- 0.85 mg/g dry wt, P less than 0.05). With the use of transmission electron microscopy, collagen fibril diameter was reduced with SVT compared with CON (1.45 +/- 0.5 vs. 1.7 +/- 0.5 microns, P less than 0.05) and increased with PST (3.3 +/- 1.4 microns, P less than 0.05). Scanning electron microscopy revealed disruption of collagen struts between adjacent SVT myocytes and a thickened collagen weave with PST. Thus chronic SVT resulted in systolic and diastolic dysfunction and reduced collagen support of adjoining myocytes. Early recovery from SVT was associated with LV hypertrophy, increased collagen, and increased LV stiffness.

Animals↗

PubMed1991

Alterations in myocyte shape and basement membrane attachment with tachycardia-induced heart failure.

Chronic supraventricular tachycardia (SVT) results in left ventricular (LV) dilatation and dysfunction. However, the underlying mechanisms responsible for LV failure in this setting are not known. LV force production is dependent on the coupling of myocytes to the extracellular matrix, which is mediated through the basement membrane. This study was designed to determine whether alterations in myocyte geometry and basement membrane attachment are associated with LV failure in a pacing-induced model of cardiomyopathy. Echocardiographic measurement of LV function was performed in six pigs after 3 weeks of pacing-induced SVT (240 beats/min) and in eight sham-operated controls. Myocytes from these hearts were isolated, and attachment studies to specific components of the basement membrane were performed using laminin, fibronectin, and collagen IV. The SVT group when compared with the control group showed a significant reduction of LV fractional shortening (14 +/- 2% versus 31 +/- 2%, respectively; p less than 0.05), increased end-diastolic dimension (50 +/- 1 versus 35 +/- 1 mm, respectively; p less than 0.05), and lengthening of isolated myocytes (196 +/- 18 versus 142 +/- 9 microns, respectively; p less than 0.05). Myocyte attachment to laminin (50 micrograms/ml) was significantly decreased at 60 minutes in the SVT group compared with the control group (18.2 +/- 4.5 versus 60.9 +/- 4.5 cells/mm2, respectively; p less than 0.05). Similar reductions in myocyte attachment to fibronectin and collagen IV were observed. Ultrastructural examination of LV sections revealed focal disruptions of the basement membrane-sarcolemmal interface and a reduced number of sarcolemmal festoons in SVT hearts compared with control hearts (0.8 +/- 0.6 versus 2.8 +/- 0.8/4 microns, respectively; p less than 0.05). These alterations in myocyte morphology and basement membrane attachment may contribute to the LV failure associated with chronic SVT. Further, these structural changes may play a significant role in the progression of ventricular dysfunction as well as recovery from chronic SVT.

Animals↗

PubMed1991

Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy.

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Termination of SVT appears to reduce LV size and improve function. However, changes in myocyte structure and morphology that accompany the development and regression of SVT-induced cardiomyopathy have not been studied. Accordingly, we measured LV function using echocardiography and catheterization in three groups of six pigs each: 3 weeks of atrial pacing (SVT; 240 beats/min), 4-week recovery from SVT (PST), and sham-operated controls. At each of these three end points, isolated myocyte dimensions and nuclear number were measured using fluorescence, and the volume percent of myocytes and myofibrils was computed from tissue sections using stereological techniques. SVT resulted in reduced LV fractional shortening (15 +/- 3% versus 31 +/- 2%, p less than 0.05), increased end-diastolic dimension (5.6 +/- 0.8 versus 3.8 +/- 0.2 cm, p less than 0.05), and no change in mass (2.6 +/- 0.1 versus 2.6 +/- 0.2 g/kg, p = NS) compared with controls. Myocyte length significantly increased with SVT (171 +/- 9 versus 109 +/- 11 microns, p less than 0.05), without significant changes in cell width (28 +/- 2 versus 26 +/- 2 microns). Nuclear number did not change with SVT; however, nuclear area/myocyte area significantly increased compared with controls (9.5 +/- 0.8 versus 8.7 +/- 0.8 x 10(-2), p less than 0.05). The volume percent of myocytes within the ventricular wall and the volume percent of myofibrils within myocytes decreased with SVT compared with controls (72 +/- 3% versus 80 +/- 3% and 45 +/- 5% versus 63 +/- 4%, respectively, p less than 0.05), with no change in total myocyte volume (54.2 +/- 2.7 versus 54.3 +/- 1.8 microns3 x 10(12)). In the PST group, LV fractional shortening returned to control values; however, there was persistent dilatation (end-diastolic dimension: 4.2 +/- 0.1 cm, p less than 0.05), and LV hypertrophy developed (3.3 +/- 0.3 g/kg, p less than 0.05). Increased myocyte length (158 +/- 5 microns, p less than 0.05) and width (33 +/- 2 microns, p less than 0.05) were observed in the PST group. The volume percent of myocytes and myofibrils returned to control values, with total myocyte volume significantly increased in the PST group compared with the control and SVT groups (74.5 +/- 2.6 microns3 x 10(12), p less than 0.05). In addition, the number of nuclei per myocyte in the PST group significantly increased from control values (5.1 +/- 0.1 versus 4.0 +/- 0.1, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Sedative and cardiovascular effects of midazolam in swine.

The ability to reliably produce sedation in swine is hampered by the paucity of agents available. This project examined the use of a new water soluble benzodiazepine, midazolam, as a sedative in swine. Echocardiographic studies were performed on thirty 23 to 30 kg Yorkshire swine before and 20 minutes after each animal received a single intramuscular dose of 100 micrograms/kg midazolam. Heart rate and respiratory rate decreased significantly compared to nonsedated values (93 +/- 7 versus 117 +/- 2 bpm and 10 +/- 1 versus 20 +/- 1 breaths/min, respectively [p less than 0.05]). However, there was no effect on left ventricular fractional shortening (29.9 greater than 0.05 versus 29.5 +/- 0.05% [p greater than 0.05]). An additional five pigs were instrumented for a dose response study in order to collect hemodynamic data and blood gas values at baseline, and 15 min after the intravenous administration of incremental doses of midazolam (100 to 1,000 micrograms/kg). Despite a significant decrease in heart rate and respiratory rate, cardiac output, blood gases, and pH remained within normal ranges at all dosage levels. Both routes of administration produced sedation for 20 min in all animals. Midazolam is an effective swine sedative that is associated with stable cardiac function.

Animals↗

PubMed1991

Effect of a LTD4 receptor antagonist in porcine septic shock.

The effect of a selective LTD4 receptor antagonist SK & F104353 was studied in septic pigs anesthetized with isoflurane. Yorkshire pigs (25.2 +/- 2.3 kg) were instrumented and monitored for cardiac output (CO), mean arterial pressure (MAP), systemic vascular resistance (SVR), mean pulmonary arterial pressure (MPAP), pulmonary vascular resistance (PVR), renal artery blood flow (RABF), renal vascular resistance (RVR), arterial PO2, and extravascular lung water (EVLW). Blood samples were also collected for platelet, white blood cell and hematocrit determinations and plasma was assayed for thromboxane (TX) B2. Sepsis was induced by infusion of Pseudomonas aeruginosa (3 x 10(8) CFU%kg/h) for 2 h. Cardiovascular and hematologic data were determined at 30 min intervals for 4 h. Groups were infused with either SK & F104353 (3 mg/kg/h; n = 5) or drug vehicle (n = 6) beginning 15 min prior to infusion with the P. aeruginosa. In the vehicle group beginning at -90 min after sepsis induction, there was a 30 +/- 7% decrease of CO, a 27 +/- 5.0% decrease of MAP, and a 44 +/- 7% decrease of RABF, whereas, MPAP increased to 147 +/- 37% and plasma TXB2 increased from less than 200 pg/ml to 3,049 +/- 367 pg/ml (P less than 0.05). The EVLW and hematocrit increased (P less than 0.05), and the arterial PO2, white blood cell count, and platelet count decreased with the severity of the sepsis. In pigs pretreated with SK & F104353 the MAP and RABF were transiently improved (P less than 0.05), and the decrease in arterial PO2 was delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Dobutamine-201Tl imaging. Assessing cardiac risks associated with vascular surgery.

The prevalence of coronary artery disease among patients considered for vascular surgical reconstructive procedures is appreciable though often clinically not apparent. One hundred and twenty-six patients underwent dobutamine-201Tl imaging (DTI) in preparation for vascular reconstruction. Fifty-four patients (43%) had a normal study and underwent vascular reconstruction, with one postoperative myocardial ischemic event (1.8%). 30 patients (24%) had a fixed defect present on DTI, which was indicative of prior infarction. Twenty-eight of these 30 patients underwent vascular reconstruction, with three postoperative myocardial ischemic events (11%, p = NS). The presence of a fixed defect on DTI did not significantly increase the risk of ischemic events in patients undergoing vascular procedures. Forty-two (33%) patients had reperfusion of their defects on DTI, which was indicative of myocardial ischemia. Fifteen of these 42 (36%) were denied vascular reconstruction. Nine of the 42 (21%) had either coronary artery bypass graft surgery or coronary angioplasty performed before vascular reconstruction without any postoperative myocardial ischemic events. The remaining 18 patients with reversible ischemia identified by DTI underwent vascular reconstruction without preoperative cardiac intervention, and nine of these 18 (50%) suffered a postoperative myocardial ischemic event (p less than 0.0001). Although there was a difference in the incidence of ischemic events among patients undergoing peripheral vascular compared with aortic reconstruction (71% versus 36%), if there was reversible ischemia identified on DTI this did not reach statistical significance. DTI is a reliable screening test that allows for an accurate means of predicting cardiac risks associated with vascular reconstruction, as well as identifying patients that might benefit from further cardiac evaluation and preoperative intervention.

Aged↗

PubMed1990

Preoperative evaluation of cardiac risk using dobutamine-thallium imaging in vascular surgery.

Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine-thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery.

Aged↗