Biomedical subjects

M Gabel

Publications and source records attributed to M Gabel.

At least 37 records · Page 2Linked to original sources

PubMed1996

Mechanism of antiarrhythmic drug-induced changes in defibrillation threshold: role of potassium and sodium channel conductance.

OBJECTIVES: We sought to determine which ion current predominantly affects defibrillation outcomes by using specific pharmacologic probes (lidocaine [a sodium channel blocking agent] and cesium [an outward potassium channel blocking agent]) in 26 swine. BACKGROUND: The effect of a drug on sodium or potassium channel conductance, or both, may affect defibrillation threshold values. However, it is unknown which ion channel predominates. METHODS: Each pig was randomly assigned to one of four treatment groups with two treatment phases: group 1 = placebo (D5W) in treatment phase I followed by placebo plus cesium in treatment phase II (n = 6); group 2 = lidocaine followed by lidocaine plus placebo (n = 7); group 3 = lidocaine followed by lidocaine plus cesium (n = 7); group 4 = placebo followed by placebo plus placebo (n = 6). Defibrillation threshold values and electrocardiographic measurements were obtained at baseline and at treatment phases I and II. RESULTS: Lidocaine increased defibrillation threshold values from baseline by 71% in group 2 (p = 0.02) and by 92% in group 3 (p < 0.01). There were no changes in defibrillation threshold values from baseline to D5W in groups 1 and 4. When D5W was added to lidocaine in group 2 and D5W in group 4, there were no significant changes in defibrillation threshold values. However, when cesium was added to lidocaine in group 3, the elevated defibrillation threshold values (mean +/- SD) returned to baseline values (from 15.7 +/- 3.46 to 7.55 +/- 3.19 J, p < 0.01). Cesium added to D5W in group 1 also significantly reduced defibrillation threshold values from 7.10 +/- 1.27 to 4.14 +/- 1.75 J (p < 0.01). The effect of cesium on defibrillation threshold values was similar between groups 1 and 3, regardless of lidocaine, such that these values were reduced by 40 +/- 14% and 51 +/- 18%, respectively (p = 0.28). CONCLUSIONS: Cesium, through potassium blockade, reverses lidocaine-induced elevation in defibrillation threshold values. The magnitude of defibrillation threshold reduction when cesium was added to lidocaine was similar to the defibrillation threshold reduction when cesium was added to placebo. Thus, inhibiting outward potassium conductance and prolonging repolarization decreases defibrillation threshold values independent of sodium channel blockade.

Animals↗

PubMed1996

Effects of thyroid hormone on left ventricular performance and regulation of contractile and Ca(2+)-cycling proteins in the baboon. Implications for the force-frequency and relaxation-frequency relationships.

The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on primate myocardium are poorly understood. Therefore, we studied the effects of thyroid hormone on sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins and myosin heavy chain (MHC) composition at the steady state mRNA and protein level and associated alterations of left ventricular (LV) performance in 8 chronically instrumented baboons. The force-frequency and relaxation-frequency relations were assessed as the response of LV isovolumic contraction (dP/dtmax) and relaxation (Tau), respectively, to incremental atrial pacing. Both the heart rate at which dP/dtmax was maximal and Tau was minimal (critical heart rates) in response to pacing were increased significantly after thyroid hormone. Postmortem LV tissue from 5 thyroid-treated and 4 additional control baboons was assayed for steady state mRNA levels with cDNA probes to MHC isoforms and SR Ca(2+)-cycling proteins. Steady state SR Ca(2+)-ATPase and phospholamban mRNA increased in the hyperthyroid state, and alpha-MHC mRNA appeared de novo, whereas beta-MHC mRNA decreased. Western analysis (4 thyroid-treated and 4 control baboons) showed directionally similar changes in MHC isoforms and a slight increase in SR Ca(2+)-ATPase. In contrast, there was a statistically nonsignificant decrease in phospholamban protein, which resulted in a significant 40% decrease in the ratio of phospholamban to SR Ca(2+)-ATPase. Thus, thyroid hormone increases the transcription of Ca(2+)-cycling proteins and shifts MHC isoform expression in the primate LV. Our data suggest that both transcriptional and posttranslational mechanisms determine the levels of these proteins in the hyperthyroid primate heart and mediate, in part, the observed enhanced basal and frequency-dependent LV performance.

Animals↗

PubMed1996

Influence of hypertonic saline solution infusion on defibrillation efficacy.

Hypertonic saline solution may enhance cardiac conduction via the fast inward sodium channel and alter transmembrane Ca+2 conductance via the sodium-calcium exchanger. Evidence suggests that both Ca+2 conductance and myocardial conduction velocity may affect ventricular defibrillation. Since hypertonic saline solution solutions (ie, sodium bicarbonate) may be administered to patients who have conditions that often require ventricular defibrillation (ie, cardiac arrest or hypovolemic shock), we studied the effect of hypertonic saline solution on the defibrillation threshold (DFT) in 16 pentobarbital-anesthetized domestic farm swine (20 to 30 kg). Defibrillation was performed using two interfaced epicardial electrode patches. DFTs were determined at baseline and during treatment phase. Pigs were randomly assigned to treatment consisting of either hypertonic saline solution (6 mmol/kg load, 2.0 to 3.0 mmol/kg infusion) to maintain serum sodium concentrations 10 to 15 mmol/L above baseline or control (D5W given in equal volume). DFT values (joules) that predicted 50% success were modeled from a best-fit histogram. Hypertonic saline solution did not change DFT values from baseline values (10.2 +/- 4.3 vs 10.8 +/- 7.0, respectively). Likewise, placebo (D5W) did not change DFT values from baseline values (10.1 +/- 4.5 vs 11.3 +/- 4.3). During treatment phase, DFT values were 99 +/- 28% of baseline values in the hypertonic saline solution group and 116 +/- 23% of baseline values in the D5W groups (p = 0.21). The administration of hypertonic saline solution also did not affect ventricular conduction velocity, right ventricular action potential duration, or right ventricular effective refractory period. These data indicate that hypertonic saline solution does not appreciably affect defibrillation efficacy or electrical treatment of ventricular fibrillation.

Animals↗

PubMed1995

Differential effects of lidocaine on defibrillation threshold with monophasic versus biphasic shock waveforms.

BACKGROUND: Defibrillation waveforms and antiarrhythmic drugs have disparate effects on myocardial excitability and refractoriness, making it likely that antiarrhythmic drugs will interact with one waveform differently than with another. The aim of the present study was to determine if the increase in defibrillation threshold (DFT) induced by lidocaine is similar for electrical shocks with monophasic and biphasic waveforms. METHODS AND RESULTS: Twenty-six pentobarbital-anesthetized farm-raised pigs were instrumented with pacing catheters and epicardial defibrillation electrodes. Each pig was assigned to one of four groups: (1) monophasic shock waveform and placebo (5% dextrose in water [D5W]) (n = 7), (2) monophasic shock waveform and lidocaine (n = 7), (3) biphasic shock waveform and placebo (D5W) (n = 5), or (4) biphasic shock waveform and lidocaine (n = 7). DFT was measured at baseline and subsequently during treatment (D5W or lidocaine). In the monophasic waveform groups, DFT increased from baseline in response to lidocaine by 92% (P < .0001), whereas DFT values in response to D5W did not change. In the biphasic waveform groups, DFT values did not change from baseline in response to lidocaine (P = NS), whereas DFT values from baseline in response to D5W significantly decreased by 29% (P = .04). In the monophasic waveform groups, the change in DFT from baseline in response to lidocaine was significantly different than the change from baseline in response to D5W (92 +/- 29% versus -0.5 +/- 29%, respectively) (P < .0002). In the biphasic waveform groups, however, the change in DFT from baseline in response to lidocaine was similar to the change from baseline in response to D5W (-5.66 +/- 15% versus -29 +/- 17%, respectively) (P = .48). Furthermore, the change in DFT from baseline in response to lidocaine differed significantly between monophasic and biphasic waveform groups (92 +/- 29% versus -5.66 +/- 15%) (P < .0002), whereas the change from baseline in response to D5W did not differ between monophasic and biphasic waveforms (-0.5 +/- 29% versus -29 +/- 17%) (P = .34). CONCLUSIONS: Compared with placebo groups, DFT values increased during lidocaine treatment to a much greater degree in the monophasic waveform group than in the biphasic waveform group receiving lidocaine. These data support our hypothesis that antiarrhythmic drugs can affect the defibrillation efficacy of monophasic waveforms differently than that of biphasic waveforms.

Animals↗

PubMed1995

Residual 201Tl activity in irreversible defects as a marker of myocardial viability. Clinicopathological study.

BACKGROUND: The objective of the present study was to characterize the relation between the residual 201Tl activity in irreversible perfusion defects and the extent of irreversible myocardial damage indicated by the volume fraction of myocardial interstitial fibrosis in patients with chronic coronary artery disease. METHODS AND RESULTS: Stress planar 201Tl scintigraphy with tracer reinjection at rest was performed in 37 patients with > or = 75% stenosis of the left anterior descending coronary artery, and anteroseptal 201Tl activity was quantified by computer-assisted placement of regions of interest from the serial myocardial images. During coronary artery bypass grafting (performed within 6 +/- 3 weeks after scintigraphy), two transmural biopsy specimens were taken from the anterior wall of the left ventricle and the amount of interstitial fibrosis was assessed by use of light microscopic morphometry. A wide spectrum of interstitial fibrosis was obtained, ranging from 15 vol% to 60 vol%. Interstitial fibrosis was similar in patients with reversible (n = 11) or irreversible (n = 15) tracer defects in conventional stress-redistribution images. However, interstitial fibrosis was significantly lower in patients who had enhanced regional 201Tl activity after tracer reinjection compared with those who did not have enhancement of tracer activity after reinjection (28 +/- 8 vol%, n = 7, versus 41 +/- 12 vol%, n = 8; P = .031). The correlation between relative poststenotic 201Tl activity and interstitial fibrosis after tracer reinjection was significantly improved compared with conventional redistribution images (r = -.622 versus r = -.851, n = 15; P < .01). CONCLUSIONS: The present data demonstrate that the level of regional 201Tl activity in redistribution and, in particular, reinjection images is significantly related to the mass of preserved viable myocytes in poststenotic left ventricular myocardium. Therefore, the residual 201Tl activity provides information about viability within irreversible perfusion defects and may itself serve as marker of myocardial viability.

Biopsy↗

PubMed1995

Disparate effects of early pressure overload hypertrophy on velocity-dependent and force-dependent indices of ventricular performance in the conscious baboon.

BACKGROUND: The effects of early pressure overload on left ventricular (LV) chamber mechanics in the primate heart are poorly understood. METHODS AND RESULTS: To test the hypothesis that early LV pressure overload hypertrophy is associated with depression of velocity-dependent indices of LV systolic (LV dP/dt) and diastolic function (time constant of relaxation, tau) but unchanged systolic elastance (Ees), we studied six conscious baboons instrumented with LV micromanometers and LV dimension and wall thickness sonomicrometers. Loading conditions were altered by pharmacological angiotensin II generation both before and 12 weeks after producing renovascular hypertension (2 kidney, 1 clip). The LV systolic pressure (149 +/- 11 [SD] versus 114 +/- 5 mm Hg) and LV mass (125 +/- 25 versus 91 +/- 20 g) were greater 12 weeks after than before (both P < .05). Both Ees and Ees normalized for LV mass were similar before versus 12 weeks after (23.0 +/- 9.6 versus 22.3 +/- 9.8 mm Hg/mL and 26.5 +/- 14.5 versus 19.8 +/- 12.5 mm Hg/mL, respectively; both P = NS). At matched LV systolic and diastolic pressures, LV fractional shortening was similar (18.6 +/- 6.8% versus 21.6 +/- 4.9%), but the time constant of LV isovolumic relaxation was significantly longer (42.3 +/- 5.3 versus 31.4 +/- 7.0 ms, P < .05) and LV dP/dt and Vcf were significantly less (1891 +/- 352 versus 2342 +/- 284 mm Hg/s and 0.9 +/- 0.4 versus 1.1 +/- 0.3 circ/s, respectively; both P < .05) 12 weeks after than before. CONCLUSIONS: In conscious baboons with systemic arterial hypertension and early LV hypertrophy, there is depression of velocity-dependent indices of LV contraction and relaxation but unaltered force-dependent measures of contractility.

Animals↗

PubMed1995

[Investigations of empty body weight gain, on protein, fat and energy disposition as well as on utilization of metabolizable energy for energy deposition in black and white bulls. 1. Empty body weight gain].

Six series of individual feeding experiments (altogether 544 animals) with different energy supply and connected with steps slaughteries and whole-body analyses, constructed carried out and analysed upon the same aspects, were regression analytically interpreted with the aim of quantify the relation of empty body weight to live weight. The relation of empty body weight to live weight showed a nonlinear dependence on the live weight as well as on the age of animals. The assessment of the metabolizability of energy of the diet as an additional variable reduced the residual variation considerably. Therefore from the knowledge of live weight or age of the animals, and the metabolizability of energy of the diet the relation of empty body weight to live weight of black and white bulls could be calculated. Moreover, the relation of empty body weight gain to live weight gain in dependence on live weight and live weight gain was investigated.

Animal Feed↗

PubMed1995

[Empty body weight gain, protein, fat and energy deposit and utilization of metabolizable energy for energy deposit in black and white bulls. 2. Protein, fat and energy deposit].

The protein, fat and energy deposition determined in 6 series of individual feeding experiments with different energy supply on slaughter steps (altogether 458 animals) and whole body analysis were generalized in this publication on nonlinear regression analyses. The protein deposition per kg empty body weight gain is influenced by empty body weight, it takes off with increase of the empty body weight. At low empty body weight (100-200 kg) the protein deposition per kg empty body weight gain is small increased with increasing of empty body weight gain, at high empty body weight it is reduced continuously. The fat deposition per kg empty body weight gain increases progressively with the empty body weight and with the empty body weight gain respectively. The energy deposition per kg empty body weight gain increases with increase of empty body weight and of empty body weight gain. It showed the same development like the fat deposition. The protein, fat and energy deposition per kg live weight gain are calculated and tabulated in dependence on the live weight and the live weight gain.

Animals↗

PubMed1995

[Empty body weight gain, protein, faty and energy deposit and utilization of metabolizable energy for energy deposit in black and white bulls. 2. Relationship between energy deposit and intake of metabolizable energy].

From 6 series of individual feeding experiments with different energy supply (EL = 1.1-1.8; EL = 538 kJ/kg LW0.75) the relationship between the intake of metabolizable energy and live weight gain empty body weight gain and energy deposition was quantified according to a nonlinear regression analysis: intake ME (MJ/d) = A.eB.ED. EBWG. LWG with A = a.LW0.75 B = b.ec.LW The estimated parameters are: [chart: see text] The regression analysis made it possible to estimate the maintenance requirement. Dependent on the variable the following values for maintenance requirements were found: [chart: see text] For the partial utilization of metabolizable energy for energy deposition an average value of 0.37 was obtained by suggestion of a maintenance requirement of 538 kJ/kg LW0.75 and a nonlinear generalization of intake of metabolizable energy. The utilization of metabolizable energy was positively influenced by the metabolizability of the energy of the diet and it was negatively influenced by the energy level. The linear quantification of the relation between the intake of metabolizable energy and the energy deposition led to an utilization of 0.40.

Animals↗

PubMed1995

Effects of angiotensin II generated by an angiotensin converting enzyme-independent pathway on left ventricular performance in the conscious baboon.

Human chymase is a serine proteinase that converts angiotensin (Ang) I to Ang II independent of angiotensin converting enzyme (ACE) in vitro. The effects of chymase on systemic hemodynamics and left ventricular function in vivo were studied in nine conscious baboons instrumented with a LV micromanometer and LV minor axis and wall thickness sonomicrometer crystal pairs. Measurements were made at baseline and after [Pro11DAla12] Ang I, a specific substrate for human chymase, was given in consecutive fashion as a 0.1 mg bolus, an hour-long intravenous infusion of 5 mg, a 3 mg bolus, and after 5 mg of an Ang II receptor antagonist. [Pro11DAla12]Ang I significantly increased LV systolic and diastolic pressure, LV end-diastolic and end systolic dimensions and the time constant of LV relaxation and significantly decreased LV fractional shortening and wall thickening. Administration of a specific Ang II receptor antagonist reversed all the hemodynamic changes. In separate studies, similar results were obtained in six of the baboons with ACE blockade (20 mg, intravenous captopril). Post-mortem studies indicated that chymase-like activity was widely distributed in multiple tissues. Thus, in primates, Ang I is converted into Ang II by an enzyme with chymase-like activity. This study provides the first in vivo evidence of an ACE-independent pathway for Ang II production.

Angiotensin I↗

PubMed1995

Left atrial mechanical and biochemical adaptation to pacing induced heart failure.

OBJECTIVE: To determine the left atrial mechanical and biochemical adaptations to congestive heart failure, 10 dogs with rapid atrial and ventricular pacing and seven control dogs were studied. METHODS: Animals were instrumented with left atrial sonomicrometers and micromanometers and left atrial pressure-volume relationships were generated by phenylephrine boluses for maximum elastance (Emax) and end systolic elastance (Ees) calculations. Left atrial maximum volume, ejection fraction, and mean circumferential fibre shortening (Vcf) were compared at matched left atrial pressure. At necropsy, myosin heavy chain (MHC) isoforms from the left atrial body and appendage were separated with SDS-PAGE, stained with monoclonal antibodies to alpha and beta MHC, and quantified with laser densitometry. RESULTS: Left atrial ejection fraction and Vcf were significantly lower and maximum atrial volume and atrial systolic stroke volume were significantly greater in heart failure than in control. Emax was not significantly altered in heart failure, at 5.9(SD 2.9) v 4.5(1.6) mm Hg.ml-1 in controls. However, Vcf was lower (P < 0.05) and the A loop pressure-volume area (an index of eternal mechanical work performed by the left atrium) was greater (P < 0.05) in heart failure than in control dogs. The percent beta MHC in the left atrial body was greater in dogs with heart failure than in controls, at 42.6(9.8) v 17.3(9.0)%, P < 0.05. By contrast there was no significant beta MHC isoform switch in the left atrial appendage [14.4(7.6) v 17.9(9.7)%]. CONCLUSIONS: In this model of left atrial pressure and volume overload, there is significant upregulation of beta MHC in the left atrial body but not in the appendage and this isoform switch is associated with decreased velocity of left atrial contraction, increased atrial mechanical work, and unchanged force generation.

Animals↗

PubMed1995

Characteristics of chronic left ventricular dysfunction induced by coronary embolization in a canine model.

We have characterized the coronary vascular reserve, left ventricular function and inotropic response in dogs with chronic heart failure consequent to intracoronary embolization (EMB) with 50 microns spheres. We conducted studies 12-39 months after embolization and contrasted the findings with normal (CON) dogs. Acute embolization produced sustained LV volume enlargement and increased wall thickness, reduction of LV ejection fraction and elevated end-diastolic pressures; resting catecholamine levels were also increased. Responses to phenylephrine, nitroprusside, and dobutamine were identical in CON and EMB and coronary vasodilator reserve was reduced despite larger coronary vascular volume. Analysis by light microscopy showed a diffuse focal and interstitial fibrosis distributed uniformly from endocardium to epicardium associated with 14% loss of myocytes. This created a functional separation of myocardial muscle bundles and a disruption of the syncytial nature of the heart. Electron microscopy of the areas of fibrosis revealed myocytes in states ranging from normal appearing, to ghosts with evidence of cytolysis and loss of the sarcolemma. This model of chronic congestive heart failure with LV systolic dysfunction and elevated LV diastolic pressures shares a number of features with the syndrome in humans.

Animals↗

PubMed1994

Estramustine: a novel radiation enhancer in human carcinoma cells.

PURPOSE: Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G2/M phase of the cell cycle. Since cells in the G2/M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. METHODS AND MATERIALS: Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S3) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. RESULTS: Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 microM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G2/M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. CONCLUSION: The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity.

Breast Neoplasms↗

PubMed1994

Clinical and biological studies of estramustine phosphate as a novel radiation sensitizer.

PURPOSE: Estramustine phosphate (EMP), a nor-nitrogen mustard carbamate derivative of estradiol-17 beta-phosphate, causes G2/M phase arrest in treated cells through its specific binding to microtubule associated proteins. Since cells in the G2/M phase are the most radiosensitive, cell culture experiments were performed to determine whether EMP would enhance the radiosensitivity of related human tumor cells. Based on the cell culture findings and well known pharmacokinetic data in humans, a Phase II prospective study of concomitant radiotherapy (RT) and EMP plus Velban for locally advanced carcinoma of the prostate was carried out. METHODS AND MATERIALS: Three established human tumor cells, DU-145 cells (prostate), MCF-7 cells (breast), and U-251 cells (malignant glioma), were used to determine cell survival curves with and without the drug. Flow cytometry was used to obtain the cell cycle distribution of cells that were exposed to the drug for periods of 1 day to 1 week. Patients with locally advanced prostate cancer (Stages B2, C, D1) were entered into the Phase II study. All patients received a total tumor dose of 65-70 Gy over 7 weeks. Oral EMP was administered daily and Velban was administered weekly, concomitantly during the course of RT. RESULTS: Radiosensitization was dependent on the exposure time and the drug concentration prior to radiation. No radiosensitization was obtained when cells were exposed to the drug after irradiation. The enhancement ratios varied from 1.3-1.6 at the 10% survival level. All patients who received the combined RT and EMP plus Velban achieved complete response (n = 27). The rate of PSA (prostate specific antigen) reduction was very prompt compared to that of the RT alone group. There was not disproportionately enhanced side effects for the combined regimen. CONCLUSION: EMP enhances radiation induced cytotoxicity in several human tumor cells in culture. The effect is most significant after prolonged exposure to the drug before irradiation. Documented G2/M phase cell cycle block by EMP is the likely mechanism of radiosensitization. The preliminary clinical findings with the combined RT and drugs are highly encouraging.

Adenocarcinoma↗

PubMed1994

Influence of acutely altered loading conditions on left atrial appendage flow velocities.

OBJECTIVES: The purpose of this study was to identify the effects of altered loading conditions on left atrial appendage flow velocities. BACKGROUND: Although studies have suggested that Doppler analysis of left atrial appendage blood flow may have clinical utility, the hemodynamic and cardiac mechanical determinants of left atrial appendage flow are poorly understood. METHODS: Transesophageal Doppler echocardiography was performed in eight atrially paced anesthetized dogs instrumented with sonomicrometers on the left atrial appendage and the left ventricular minor axis and with left atrial and left ventricular micromanometers. Left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively, were measured using volume expansion and phenylephrine infusion. RESULTS: Volume infusion caused a significant decrease in the early to late emptying and filling ratios (mean +/- SD 0.85 +/- 0.24 vs. 0.46 +/- 0.17 and 0.80 +/- 0.50 vs. 0.40 +/- 0.20, both p < 0.05). By contrast, phenylephrine infusion did not significantly alter either filling or emptying ratio. The independent determinants of each flow wave were identified with multiple regression analysis: early emptying velocity--time constant of left ventricular relaxation, left ventricular end-systolic dimension and aortic pressure (r = 0.75, p < 0.001); late emptying velocity--left ventricular peak positive time derivative of left ventricular pressure (dP/dt) and fractional shortening (r = 0.74, p < 0.001); early filling velocity--left atrial appendage shortening fraction (r = 0.45, p = 0.01) and late filling velocity--left atrial appendage lengthening rate and left ventricular fractional shortening (r = 0.56, p < 0.01). CONCLUSIONS: These results indicate that 1) both the magnitude and the pattern of left atrial appendage emptying and filling velocities are dependent on loading conditions, and 2) left atrial appendage velocities are influenced to a greater extent by changes in left ventricular than in left atrial appendage function. These findings may have implications for the pathogenesis of left atrial appendage thrombi.

Animals↗

PubMed1994

Kinetic properties of 99mTc-Q12 in canine myocardium.

BACKGROUND: 99mTc-Q12 is a new Tc(III) perfusion imaging agent that permits prompt myocardial visualization in humans. We postulated that 99mTc-Q12 myocardial activity is related to actual myocardial blood flow during conditions of myocardial ischemia and pharmacological coronary artery vasodilation and that 99mTc-Q12 shows little or no myocardial redistribution as long as 4 hours after intravenous injection. METHODS AND RESULTS: In seven anesthetized, open chest dogs, the left circumflex coronary artery was occluded, and dipyridamole (0.32 or 0.56 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q12. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized, and a total of 315 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was determined, and myocardial blood flow was calculated. 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 2 mL.g-1 x min-1 by the relation y = 0.64x + 0.35 (r = .88, P = .0001). In 14 additional anesthetized, open chest dogs, an occluder was placed around the left circumflex coronary artery, and an ischemic level of circumflex blood flow was maintained constant over 4 hours as measured by an ultrasonic flowmeter. Dipyridamole (0.56 mg/kg) was infused intravenously beginning 15 minutes after coronary occlusion and then followed by 10 mCi of 99mTc-Q12. Gamma camera images, hemodynamics, microsphere blood flow, and endocardial biopsies (latter in six dogs) were performed at 30, 60, 120, and 240 minutes after 99mTc-Q12 injection. Myocardial blood flow in the distribution of the left anterior descending artery decreased by 29.6% from 30 to 240 minutes (P < .05), whereas left circumflex blood flow increased by 40.4% from 30 to 120 minutes (P < .05) as the dipyridamole hemodynamic effects dissipated. Nevertheless, the ratio of myocardial perfusion defect zone counts to normal myocardial zone counts remained constant over 4 hours, as did the technetium counts from the needle biopsy endocardial samples. CONCLUSIONS: Over a limited range of myocardial blood flows from 0 to approximately 2 mL.g-1 x min-1, 99mTc-Q12 myocardial activity is related to actual myocardial flow at the time of tracer injection. 99mTc-Q12 shows no evidence of myocardial redistribution.

Animals↗

PubMed1994

In vivo assessment of left atrial contractile performance in normal and pathological conditions using a time-varying elastance model.

BACKGROUND: Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo. METHODS AND RESULTS: Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2, .92 to .99). There were significant time-dependent increases in the slopes [E(t)] and small but statistically insignificant decreases in the volume axis intercepts [VO(t)] of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA volume). Emax was not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL, P < .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/- 1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals. CONCLUSIONS: We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E(t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads.

Animals↗

PubMed1994

Myocardial uptake and kinetic properties of technetium-99m-Q3 in dogs.

UNLABELLED: We postulated that 99mTc-Q3, a cationic imaging agent, produces myocardial activity related to myocardial blood flow during myocardial ischemia and pharmacologic coronary artery vasodilation, and shows little or no myocardial redistribution over 4 hr after intravenous injection. METHODS: In six Group 1 dogs, the chest was opened, the left circumflex coronary artery was acutely ligated, and dipyridamole (0.32, 0.56 or 0.84 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q3. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized and 357 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was counted and myocardial blood flow calculated. In nine Group 2 dogs, a variable occluder was placed around the left circumflex coronary artery and an ischemic level of circumflex blood flow was maintained constant over 4 hr as measured by an ultrasonic flow meter. Dipyridamole (0.56 mg/kg) was then infused into the right atrium followed by 10 mCi of 99mTc-Q3. Gamma camera images were acquired at 5, 15, 30, 60, 120 and 240 min following 99mTc-Q3 injection. Microsphere blood flow and endocardial biopsies (n = 6 dogs) were performed at 30, 60, 120 and 240 min following 99mTc-Q3 injection. RESULTS: In the Group 1 animals, 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 6.1 ml/min/g by the relationship y = 0.83X + 0.18, r = 0.95, p = 0.0001. The scintigraphic ratio of myocardial perfusion defect zone counts-to-normal myocardial zone counts (0.54 +/- 0.05 at 30 min) remained constant over 4 hr, as did technetium counts from direct endocardial sampling. Scintigraphic count ratios allowed discrimination between perfusion defect and normal myocardial regions beginning at 5 min following 99mTc-Q3 injection. CONCLUSIONS: Over a range of myocardial blood flows from 0 to 6.1 ml/min/g, 99mTc-Q3 myocardial activity is related to myocardial flow at the time of tracer injection. Technetium-99m-Q3 shows no evidence of myocardial redistribution over a 4-hr period.

Animals↗