Biomedical subjects

J L Zellner

Publications and source records attributed to J L Zellner.

13 recordsLinked to original sources

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.

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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.

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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)

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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.

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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)

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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↗

PubMed1990

Bioimpedance: a novel method for the determination of extravascular lung water.

Extravascular lung water (EVLW) can be measured using the double indicator dilution technique (DD). However, because this method is highly invasive and complicated, its clinical used has been limited. In theory, changes in thoracic conductivity, or bioimpedance (BI), can reflect changes in EVLW. However, past studies were unable to directly quantitate changes in EVLW since the contribution of dynamic variables such as ventricular volumes, hematocrit (HCT), and EVLW to this impedance signal could not be discerned. Recent studies have shown that a thermodilution pulmonary artery catheter mounted with a fast response thermistor accurately measures right ventricular end-diastolic volume (RVEDV). With changes in the RVEDV and HCT known, the contribution of EVLW to the bioimpedance signal may be isolated and used to more directly measure changes in EVLW. This hypothesis was tested by creating acute sepsis in seven pigs by infusion of Pseudomonas aeruginosa. Changes in EVLW from baseline were measured using DD at 30 min and at 1, 2, and 4 hr and compared with the change in EVLW computed from a mathematical model comprising the measured changes in BI, RVEDV, and HCT at the same time points. Changes in EVLW using DD and BI were significantly correlated over the length of the study (r = 0.85, P less than 0.01). In early sepsis (30 min), BI overestimated EVLW when compared with DD (P less than 0.05). However, at 1, 2, and 4 hr there was no significant difference between the two methods. In conclusion, the use of bioimpedance and a volumetric catheter may provide a relatively simple and reliable method for continuously monitoring changes in EVLW in the intensive care setting.

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PubMed1990

Thermodilution right ventricular ejection fraction. Catheter positioning effects.

Right ventricular (RV) ejection fractions have been difficult to estimate clinically. It has been demonstrated recently that RV ejection fractions can be calculated by thermodilution techniques using a rapid response thermistor and computer. This method critically depends on adequate mixing of the thermal bolus and sensing of the rapid response thermistor. This study examined the effects of the thermistor position within the pulmonary artery and injectate site within the right atrium on RV thermodilution ejection fraction measurements. Ten pigs were instrumented with a RV thermodilution catheter in the pulmonary artery, an injectate catheter in the right atrium, an atrial-pacing electrode, and a systemic arterial catheter. The RV ejection fractions were determined using thermodilution in two ways: (1) with incremental increases in pulmonic valve to thermistor distance, and (2) with incremental increases in injectate port to tricuspid valve. These measurements were obtained at a paced rate of 107 +/- 1 beats per minute (bpm) and then repeated with pacing-induced tachycardia (140 bpm). The highest RV ejection fraction with the lowest coefficient of variation was with the thermistor 2 cm from the pulmonic valve (50 +/- 2 percent), with a significant decline from this value at 10 cm (42 +/- 4 percent, p less than 0.05). This reduction in RV ejection fraction values with increased pulmonic valve to thermistor distance became more pronounced with tachycardia where a significant decline in RV ejection fraction occurred at 4 cm from the valve when compared with 0 cm (38 +/- 6 percent vs 47 +/- 3 percent, respectively, p less than 0.05). There was no significant change in RV ejection fraction at any injectate port to tricuspid valve distance at the lower heart rate. With tachycardia, however, a significant decline in RV ejection fraction occurred with the injectate port located 7 cm from the tricuspid valve (p less than 0.05). These results demonstrate that RV ejection fractions can be reliably obtained using thermodilution. Positioning of the thermodilution catheter is an important consideration for obtaining optimal RV ejection fraction measurements. Care should be taken to position the catheter with the thermistor a minimal distance from the pulmonic valve and the injectate port within the central body of the right atrium.

Animals↗

PubMed1990

Hemodynamic effects of leukotriene (LT) D4 and a LTD4 receptor antagonist in the pig.

Vascular bed reactivity to exogenous LTD4 and blockade of these responses by a selective LTD4 receptor antagonist, SK&F 104353, were studied. Yorkshire pigs (N = 13; 25.8 +/- 1.4 kg) were anesthetized with isoflurane, and monitored for cardiac output (CO), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right ventricular stroke work (RVSW), mean arterial pressure (MAP), renal artery blood flow (RABF), pulmonary vasculature resistance (PVR), renal vascular resistance (RVR), and systemic vascular resistance (SVR). LTD4 (0.03, 0.1, 0.3, 1, 3 and 10.0 micrograms/kg) was given intravenously. The MPAP, MAP, and RABF were recorded at baseline and for 20 min after the injection of LTD4. SK&F 104353 was infused (3 mg/kg/h, i.v.) and the dose-response to LTD4 was repeated. LTD4 induced changes in the MPAP, PCWP, MAP, and RABF. SK&F 104353 attenuated LTD4 induced changes in the MPAP, PVR, RABF and RVSW. MPAP was increased 123 +/- 24% and 115 +/- 10%, respectively, in pigs given 3.0 and 10 micrograms/kg doses, and increased to only 36 +/- 9% at a 10 micrograms/kg dose of LTD4 in animals pretreated with SK&F 104353 (P less than 0.05). MPAP was not increased at the 3.0 micrograms/kg dose, and increased to only 36 +/- 9% at a 10 micrograms/kg dose of LTD4 in animals pretreated with SK&F 104353 (P less than 0.05). These changes were paralleled by a reduction in PVR. RABF was decreased 76 +/- 5% and 83 +/- 7%, respectively, at the 3.0 and 10 micrograms/kg dose of LTD4.(ABSTRACT TRUNCATED AT 250 WORDS)

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