Relationship between catheter forces, lesion characteristics, "popping," and char formation: experience with robotic navigation system.

INTRODUCTION: Popping, char and perforation are complications that can occur following catheter ablation. We measured the amount of grams (g) applied to the endocardium during ablation using a sensor incorporated in the long sheath of a robotic system. We evaluated the relationship between lesion formation, pressure, and the development of complications. METHODS: Using a robotic navigation system, lesions were placed in the left atrium (LA) at six settings, using a constant duration (40 seconds) and flow rate of either 17 cc/min or 30 cc/min with an open irrigated catheter (OIC). Evidence of complications was noted and lesion location recorded for later analysis at necropsy. RESULTS: Lesions using 30 Watts (W) were more likely to be transmural at higher (>40 g) than lower (<30 g) pressures (75% vs 25%, P < 0.001). Significantly higher number of lesions using >40 g of pressure demonstrated "popping" and crater formation as compared with lesions with 20-30 g of pressure (41% vs 15%, P = 0.008). A majority of lesions placed using higher power (45 W) with higher pressures (>40 g) were associated with char and crater formation (66.7%). No lesions using 10 g of pressure were transmural, regardless of the power. Lesions placed with a power setting less than 35 W were more likely to result in "relative" sparing of the endocardial surface than lesions at a power setting higher than 35 W (62% vs 33.3%, P = 0.02) regardless of the pressure. CONCLUSIONS: When using an OIC, lower power settings (

Esophageal luminal temperature measurement underestimates esophageal tissue temperature during radiofrequency ablation within the canine left atrium: comparison between 8 mm tip and open irrigation catheters.

INTRODUCTION: Evaluation of luminal temperature during left atrial ablation is used clinically; however, luminal temperature does not necessarily reflect temperature within the esophageal wall and poses a risk of atrioesophageal fistula. This animal study evaluates luminal esophageal temperature and its relation to the temperature of the external esophageal tissue during left atrial lesions using the 8 mm solid tip and the open irrigated tip catheters (OIC). METHODS AND RESULTS: A thermocouple was secured to the external surface of the esophagus at the level of the left atrium of the dogs. Luminal esophageal temperature was measured using a standard temperature probe. In four randomized dogs, lesions were placed using an 8 mm solid tip ablation catheter. In six randomized dogs, lesions were placed using the 3.5 mm OIC. The average peak esophageal tissue temperature when using the OIC was significantly higher than that of the 8 mm tip catheter (88.6 degrees C +/- 15.0 degrees C vs. 62.3 degrees C +/- 12.5 degrees C, P < 0.05). Both OIC and 8 mm tip catheter had significantly higher peak tissue temperatures than luminal temperatures (OIC: 88.6 degrees C +/- 15.0 degrees C vs 39.7 degrees C +/- 0.82 degrees C, P < 0.05) (8 mm: 62.3 degrees C +/- 12.5 degrees C vs 39.0 +/- 0.5 degrees C, P < 0.05). Both catheters achieved peak temperatures faster in the tissue as compared to the lumen of the esophagus, although the tissue temperature peaked significantly faster for the OIC (OIC: 25 seconds vs 90 seconds, P < 0.05) (8 mm: 63 seconds vs 105 seconds, P < 0.05). CONCLUSION: Despite the significant difference in actual tissue temperatures, no significant difference was observed in luminal temperatures between the OIC and 8 mm tip catheter.

Preclinical biocompatibility assessment of the EVAHEART ventricular assist device: coating comparison and platelet activation.

Thromboembolism and bleeding remain significant complications of ventricular assist device (VAD) support. Increasing the amount of biocompatibility data collected during preclinical studies can provide additional criteria to evaluate device refinements, while design changes may be implemented before entering clinical use. Twenty bovines were implanted with the EVAHEART centrifugal VAD for durations from 30 to 196 days. Titanium alloy pumps were coated with either diamond-like carbon or 2-methoxyethyloylphosphoryl choline (MPC). Activated platelets and platelet microaggregates were quantified by flow cytometry, including two new assays to quantify bovine platelets expressing CD62P and CD63. Temporally, all assays were low preoperatively, then significantly increased following VAD implantation, before declining to a lower, but still elevated level over 2-3 weeks. MPC-coated VADs produced significantly fewer activated platelets after implant trauma effects diminished. Three animals receiving no postoperative anticoagulation had similar amounts of circulating activated platelets and platelet microaggregates as animals receiving warfarin anticoagulation. Two new methods to quantify bovine activated platelets using antibodies to CD62P and CD63 were characterized and applied. These measures, along with previously described assays, were able to differentiate between two biocompatible coatings and assess effects of anticoagulation regimen in VAD preclinical testing.

Predicted hemodynamic benefits of counterpulsation therapy using a superficial surgical approach.

A volume-displacement counterpulsation device (CPD) intended for chronic implantation via a superficial surgical approach is proposed. The CPD is a pneumatically driven sac that fills during native heart systole and empties during diastole through a single, valveless cannula anastomosed to the subclavian artery. Computer simulation was performed to predict and compare the physiological responses of the CPD to the intraaortic balloon pump (IABP) in a clinically relevant model of early stage heart failure. The effect of device stroke volume (0-50 ml) and control modes (timing, duration, morphology) on landmark hemodynamic parameters and the LV pressure-volume relationship were investigated. Simulation results predicted that the CPD would provide hemodynamic benefits comparable to an IABP as evidenced by up to 25% augmentation of peak diastolic aortic pressure, which increases diastolic coronary perfusion by up to 34%. The CPD may also provide up to 34% reduction in LV end-diastolic pressure and 12% reduction in peak systolic aortic pressure, lowering LV workload by up to 26% and increasing cardiac output by up to 10%. This study demonstrated that the superficial CPD technique may be used acutely to achieve similar improvements in hemodynamic function as the IABP in early stage heart failure patients.

Development and early testing of a simple subcutaneous counterpulsation device.

The intra-aortic balloon pump has been widely and successfully used as a treatment for cardiac dysfunction, but it only has short-term applications. To overcome this limitation, a superficial counterpulsation device (CPD) is being developed to provide extended counterpulsation support to promote myocardial recovery. The CPD is a valveless, monoport, pneumatically driven, 40-ml sac that is intended to be implanted in a pacemaker-type pocket in the subclavian fossa. The sac is designed to fill in systole and empty during diastole through an outflow graft anastomosed to the subclavian artery. A feasibility study was conducted to investigate acute hemodynamic responses to the CPD in eight calves with diminished cardiac function. The CPD augmented aortic diastolic pressure, reduced left ventricular peak systolic and aortic ejection pressures by up to 18%, and increased diastolic coronary flow by up to 21% and stroke volume by up to 12%. A cadaver fit study demonstrated that the human subclavian artery is a reasonable anastomosis site to consider and that the 40-ml CPD needs to be reduced in size to provide a better anatomical fit. The clinical attractiveness of this approach is that it may provide extended support through a subcutaneous surgical procedure.

Monensin toxicosis in the domestic bovine calf: a large animal model of cardiac dysfunction.

A large animal with diminished cardiac function would be desirable for chronic testing of pathophysiologic responses to many human-sized devices and other therapies, especially if this model did not require prior surgical interventions or extensive technical skill and expense. Overdoses of monensin, widely used in the cattle industry as a growth promotant, are cardiotoxic, suggesting its possible use in creating cardiomyopathy. We gave a single oral dose of monensin (20 to 40 mg/kg) to 13 calves (55 to 90 kg) to produce diminished cardiac function. Hemodynamics and cardiac geometry were monitored for as long as 21 days postinduction. Within 3 days, there were signs of decreased cardiac function, as evidenced by a 10- to 20-mm Hg decrease in peak systolic blood pressure (P < 0.01 versus baseline) and a 2- to 9-mm Hg increase in central venous pressure (P < 0.01 versus baseline). There was a trend towards an increase in left ventricular end-systolic lumen diameter. Compared with those of similar-sized normal animals, stroke volume was 42% lower (P < 0.05), left atrial pressure was 67% higher (P < 0.01), and end-diastolic left ventricular pressure was 143% higher (P < 0.05). Histopathologic analysis showed extensive cardiomyocyte death. These results suggest that monensin could provide a simple, noninvasive, inexpensive, and likely irreversible means of producing clinically relevant diminished cardiac function in a human-sized animal model.

Arterial heparan sulfate is negatively associated with hyperglycemia and atherosclerosis in diabetic monkeys.

BACKGROUND: Arterial proteoglycans are implicated in the pathogenesis of atherosclerosis by their ability to trap plasma lipoproteins in the arterial wall and by their influence on cellular migration, adhesion and proliferation. In addition, data have suggested an anti-atherogenic role for heparan sulfate proteoglycans and a pro-atherogenic role for dermatan sulfate proteoglycans. Using a non-human primate model for human diabetes, studies examined diabetes-induced changes in arterial proteoglycans that may increase susceptibility to atherosclerosis. METHODS: Control (n = 7) and streptozotocin-induced diabetic (n = 8) cynomolgous monkeys were assessed for hyperglycemia by measurement of plasma glycated hemoglobin (GHb). Thoracic aortas obtained at necropsy, were extracted with 4 M guanidine HCL and proteoglycans were measured as hexuronic acid. Atherosclerosis was measured by enzymatic analysis of extracted tissue cholesterol. Glycosaminoglycan chains of arterial proteoglycans were released with papain, separated by agarose electrophoresis and analysed by scanning densitometry. RESULTS: Tissue cholesterol was positively associated with hexuronic acid content in diabetic arteries (r = .82, p < .025) but not in control arteries. Glycosaminoglycan chain analysis demonstrated that dermatan sulfate was associated with increased tissue cholesterol in both control (r = .8, p < 0.05) and diabetic (r = .8, p < .025) arteries, whereas a negative relationship was observed between heparan sulfate and tissue cholesterol in diabetic arteries only (r = -.7, p < .05). GHb, which was significantly higher in diabetic animals (8.2 +/- 0.9 vs 3.8 +/- 0.2%, p < .0005) was negatively associated with heparan sulfate in diabetic arteries (r = -.7, p < .05). CONCLUSIONS: These data implicate hyperglycemia induced modifications in arterial proteoglycans that may promote atherosclerosis.

Platelet activation, aggregation, and life span in calves implanted with axial flow ventricular assist devices.

BACKGROUND: A variety of rotary blood pumps are under development worldwide to serve as chronic ventricular assist devices (VADs). Historically VADs have been associated with thrombotic and thromboembolic complications, yet the ability to evaluate the thrombotic process in preclinical device testing has been limited. METHODS: We have developed and applied flow cytometric assays for activated platelets, platelet microaggregates, and platelet life span and consumption to calves implanted with an axial flow VAD and calves undergoing a sham surgical procedure. RESULTS: Surgical sham calves had significant increases in circulating activated platelets (p < 0.05) that resolved within 17 days, and no increases in circulating platelet microaggregates. Calves with uneventful VAD implant periods had early transient elevations in platelet microaggregates and prolonged elevations in activated platelets that did not recover to preoperative values during the study. Daily platelet consumption in VAD implanted calves was increased by 20% +/- 3%. Calves with thrombotic deposition within the VAD and elevated thromboembolism observed at autopsy experienced increases in circulating activated platelets and microaggregates at the end of the implant period when VAD flow decreased. CONCLUSIONS: This study demonstrates the ability of flow cytometry-based platelet assays to differentiate VAD implant operations from VAD support, and suggests differences that exist between uneventful VAD support and support with complications. These techniques should have value in evaluating other cardiovascular devices undergoing preclinical testing and provide insight into the temporal impact of these devices on the hemostatic system.

Smooth muscle cell hypertrophy of renal cortex arteries with chronic continuous flow left ventricular assist.

BACKGROUND: Pathophysiology of long-term continuous flow left ventricular assist is not well described. With many of these devices becoming available, it is important to examine for possible pathologic effects. In this study we examined the relationship between diminished pulsatility and pathologic changes in renal cortical arteries. METHODS: Twenty-nine calves were implanted with various continuous flow left ventricular assist systems in a left ventricle-descending thoracic aorta bypass configuration. Pulsatility was quantified by pulse pressure and pulsatility index. Pathologic changes of the renal cortex arteries were described and evaluated by medial thickness, medial/vascular cross-sectional area ratio, and smooth muscle cell count, to quantify hypertrophy or hyperplasia. Seven calves, which underwent a sham-implant, were used as controls. RESULTS: Systolic arterial pressure, pulse pressure, and pulsatility index were significantly lower and diastolic pressure was significantly higher than before implant in pump-implanted animals. Twenty-three of 29 pumpimplanted calves (79.3%) had medial smooth muscle cell hypertrophy in renal cortex arteries, whereas none of sham-implanted calves had any abnormal lesions. When the pump-implanted calves were grouped according to the presence of smooth muscle cell hypertrophy, there was a clear trend toward lower pump flow rate in calves with lesions. Renal function was within the normal range in all calves. CONCLUSIONS: There appears to be a relationship between smooth muscle cell hypertrophy in renal cortex arteries and continuous flow left ventricular assist. Furthermore, although the pathologic changes are likely multifactorial, these lesions appear to be related to lower pump assist rates.

Distal thoracic aorta hemodynamics during exercise with continuous flow left ventricular assist system.

OBJECTIVES: Continuous flow left ventricular assist systems (LVAS) are being discussed as a destination therapy. LVAS patients will have expanded activity of daily life, including exercise. In this study, we analyzed the effects of exercise on blood flow in the distal thoracic aorta of LVAD implanted animals. METHODS: Five calves with a continuous flow LVAS exercised on treadmill at two different pump flow rates (PFR), 60-80% (high PFR) and 25-30% (low PFR) of pulmonary artery flow rate. Pump, pulmonary artery and descending thoracic aorta flow waves were recorded before, during and after exercise. Systolic and diastolic flow volume in each cardiac cycle in pump and descending thoracic aorta flow was calculated. RESULTS: (1) Average flow rates - Pulmonary artery and descending thoracic aorta flow rates increased with heart rate during exercise and there was no difference between groups. (2) Pump flow wave - Pump regurgitation increased temporally during exercise at both PFRs, but sustained incidences of regurgitation after exercise were only observed at low PFR. Systolic and diastolic pump flow volume decreased during exercise at both PFRs, but systolic volume increased and diastolic volume decreased significantly after exercise at low PFR. (3) Descending thoracic aorta flow wave - At high PFR, systolic volume of descending thoracic aorta increased but diastolic flow volume decreased during exercise. At low PFR, both systolic and diastolic volume of the descending thoracic aorta decreased during exercise, but systolic volume increased and diastolic volume decreased after exercise. Systolic volume of the descending thoracic aorta in low PFR was significantly greater and diastolic volume was less than those in high PFR during and after exercise. CONCLUSION: Exercise temporarily increases pump regurgitation with continuous flow LVAS support. Average flow rate of the descending thoracic aorta was maintained by compensation from increased heart rate, although the diastolic flow of the descending thoracic aorta decreased after exercise at the lower pump flow rate. Further study will be needed to evaluate whether or not this flow decrease causes hemodynamic and/or an oxygen delivery mismatch to peripheral tissue.

Effects of left ventricular assist device support and outflow graft location upon aortic blood flow.

Although continuous flow (CFVAD) and pulsatile (PVAD) ventricular assist devices (VADs) are being clinically used, their effects upon aortic blood flow as a measure of overall blood distribution remain unclear. The objective of this study was to compare the effects of CFVAD and PVAD support for ascending (AscA) and descending (DA) aorta outflow cannulation upon mean aortic blood flow and waveform morphology. Six experiments were conducted in a normal, acute calf model, in which an inflow cannula was implanted in the left ventricle apex and outflow cannulae were anastomosed to both the AscA and DA. Flow probes were placed around the pulmonary artery, pump outflow, brachiocephalic trunk, and aorta proximal and distal to the DA outflow. For each acute experiment, calves received randomly selected levels of VAD support (0-100% of cardiac output) and pump failure (VAD off and outflow cannula unclamped) for each of four randomly selected test conditions: (1) PVAD and AscA, (2) PVAD and DA, (3) CFVAD and AscA, and (4) CFVAD and DA. Regardless of pump type or support level, proximal and distal aorta mean flows were lower (p < 0.05) for DA compared with the AscA. No differences in mean aortic flows between pump types at either outflow graft location were discerned. Differences in morphologic features of blood flow waveforms between PVAD and CFVAD were observed. During simulated pump failure, retrograde aortic blood flow in both the aortic arch and DA was observed. Partial ventricular suction was also observed during the greatest levels of CFVAD support and suggested pronounced effects upon both the right and left ventricle. Collectively, these findings imply that VAD outflow location may have an important role in patient response and recovery. Investigation of the long-term pathophysiologic responses to pump type and outflow location is ongoing.

Hemodynamic and pressure-volume responses to continuous and pulsatile ventricular assist in an adult mock circulation.

This study investigated the hemodynamic and left ventricular (LV) pressure-volume loop responses to continuous versus pulsatile assist techniques at 50% and 100% bypass flow rates during simulated ventricular pathophysiologic states (normal, failing, recovery) with Starling response behavior in an adult mock circulation. The rationale for this approach was the desire to conduct a preliminary investigation in a well controlled environment that cannot be as easily produced in an animal model or clinical setting. Continuous and pulsatile flow ventricular assist devices (VADs) were connected to ventricular apical and aortic root return cannulae. The mock circulation was instrumented with a pressure-volume conductance catheter for simultaneous measurement of aortic root pressure and LV pressure and volume; a left atrial pressure catheter; a distal aortic pressure catheter; and aortic root, aortic distal, VAD output, and coronary flow probes. Filling pressures (mean left atrial and LV end diastolic) were reduced with each assist technique; continuous assist reduced filling pressures by 50% more than pulsatile. This reduction, however, was at the expense of a higher mean distal aortic pressure and lower diastolic to systolic coronary artery flow ratio. At full bypass flow (100%) for both assist devices, there was a pronounced effect on hemodynamic parameters, whereas the lesser bypass flow (50%) had only a slight influence. Hemodynamic responses to continuous and pulsatile assist during simulated heart failure differed from normal and recovery states. These findings suggest the potential for differences in endocardial perfusion between assist techniques that may warrant further investigation in an in vivo model, the need for controlling the amount of bypass flow, and the importance in considering the choice of in vivo model.

Effects of continuous flow left ventricular assist device support on skin tissue microcirculation and aortic hemodynamics.

Continuous flow ventricular assist devices (CFVADs) are thought to be the next generation of circulatory assist devices. With many now in various stages of development or clinical trial, it is important that the physiologic aspects of these pumps be critically analyzed. In this study, 15 calves were divided into two groups. One group received a CFVAD, and the other a sham implant. Two additional animals were used in an acute study to examine aortic blood flow patterns from a CFVAD. Tissue perfusion was measured on all animals before surgery and then weekly thereafter. Before surgery, there was no difference in hemodynamics or tissue perfusion between studied animals. Postoperatively, CFVAD animals had statistically significant increased diastolic pressure. Significantly decreased pulse pressure, pulse index, and tissue perfusion were also observed in CFVAD animals. Results from the flow pattern studies suggested that at moderate levels of pump support (40-75%), the amount of blood flow distal to the outflow graft anastomosis decreased approximately 25% because of increased regurgitant blood flow in the aorta. These results suggest that the diminished tissue perfusion is likely due to changes in aortic hemodynamics and provide some insight into the distribution of flow from CFVADs.

Left ventricular and myocardial perfusion responses to volume unloading and afterload reduction in a computer simulation.

Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. In a few cases, patients have been successfully weaned from these devices after myocardial recovery. To promote myocardial recovery and alleviate the demand for donor organs, we are developing an artificial vasculature device (AVD) that is designed to allow the heart to fill to its normal volume but eject against a lower afterload. Using this approach, the heart ejects its stroke volume (SV) into an AVD anastomosed to the aortic arch, which has been programmed to produce any desired afterload condition defined by an input impedance profile. During diastole, the AVD returns this SV to the aorta, providing counterpulsation. Dynamic computer models of each of the assist devices (AVD, continuous, and pulsatile flow pumps) were developed and coupled to a model of the cardiovascular system. Computer simulations of these assist techniques were conducted to predict physiologic responses. Hemodynamic parameters, ventricular pressure-volume loops, and vascular impedance characteristics were calculated with AVD, continuous VAD, and asynchronous pulsatile VAD support for a range of clinical cardiac conditions (normal, failing, and recovering left ventricle). These simulation results indicate that the AVD may provide better coronary perfusion, as well as lower vascular resistance and elastance seen by the native heart during ejection compared with continuous and pulsatile VAD. Our working hypothesis is that by controlling afterload using the AVD approach, ventricular cannulation can be eliminated, myocardial perfusion improved, myocardial compliance and resistance restored, and effective weaning protocols developed that promote myocardial recovery.

Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments.

Over the past several decades, blood-soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG-3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG-200), which possesses no drag-reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two-hour survival rate, the latter from 19% (Control) and 14% (PEG-200) to 100% (AVP) and 100% (PEG-3500). Furthermore, the Control and PEG-200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG-3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.

Accelerative forces associated with routine inhouse transportation of rodent cages.

Transportation of rodents has repeatedly been demonstrated to potentially affect research outcomes. In addition, rapid acceleration and deceleration have marked physiologic effects. The current study determined the accelerative forces associated with common types of animal transportation within the institution and means of reducing these effects. A rodent-sized (24 g) accelerometer was placed in a standard polycarbonate mouse cage, which then was hand-carried or loaded onto a plastic, small metal, or large metal cart. The cage then moved along a set path that included several flooring types and obstacles. Accelerative forces within the mouse cage varied by as much as 35 m/s(2) in as little as 1 s, primarily along the vertical axis (Z-axis). Measured acceleration was greatest with the plastic cart and lowest during hand-carrying. The placement of a towel under the cage dampened in-cage acceleration due to cart use by more than 50%, whereas a similarly located underpad had no significant effect. These data document that small rodents typically are exposed to considerable motion during transportation. The resulting physical and physiologic effects could affect study outcomes.

Hemodynamic responses to continuous versus pulsatile mechanical unloading of the failing left ventricle.

Debate exists regarding the merits and limitations of continuous versus pulsatile flow mechanical circulatory support. To characterize the hemodynamic differences between each mode of support, we investigated the acute effects of continuous versus pulsatile unloading of the failing left ventricle in a bovine model. Heart failure was induced in male calves (n = 14). During an acute study, animals were instrumented through thoracotomy for hemodynamic measurement. A continuous flow (n = 8) and/or pulsatile flow (n = 8) left ventricular assist device (LVAD) was implanted and studied during maximum support ( approximately 5 L/min) and moderate support ( approximately 2-3 L/min) modes. Pulse pressure (PP), surplus hemodynamic energy (SHE), and (energy equivalent pressure [EEP]/mean aortic pressure (MAP) - 1) x 100% were derived to characterize hemodynamic energy profiles during the different support modes. Standard hemodynamic parameters of cardiac performance were also derived. Data were analyzed by repeated measures one-way analysis of variance within groups and unpaired Student's t-tests across groups. During maximum and moderate continuous unloading, PP, SHE, and (EEP/MAP - 1) x 100% were significantly decreased compared with baseline and compared with pulsatile unloading. As a result, continuous unloading significantly altered left ventricular peak systolic pressure, aortic systolic and diastolic pressure, +/-dP/dt, and rate x pressure product, whereas pulsatile unloading preserved a normal profile of physiologic values. As continuous unloading increased, the pressure-volume relationship collapsed, and the aortic valve remained closed. In contrast, as pulsatile unloading increased, a comparable decrease in left ventricular volumes was noted. However, a normal range of left ventricular pressures was preserved. Continuous unloading deranged the physiologic profile of myocardial and vascular hemodynamic energy utilization, whereas pulsatile unloading preserved more normal physiologic values. These findings may have important implications for chronic LVAD therapy.

A pilot study for inducing chronic heart failure in calves by means of oral monensin.

INTRODUCTION: Heart failure remains a major cause of mortality in the United States, despite advancing technologies, newer methods of treatment, and novel devices. To evaluate such novel devices, a large-animal model of chronic heart failure is critical in carrying out preclinical animal studies. METHODS: We evaluated the efficacy of oral monensin in inducing stable heart failure in five Jersey calves. Various doses of monensin were administered. Hemodynamics, pressure-volume loops, echocardiographic measurements, extent of tissue perfusion, and histopathologic data were recorded before and after induction of heart failure. RESULTS: Responses were variable in the animals. One experiment showed a significant decrease in cardiac output within one week, associated with simultaneous increases in left atrial pressure, central venous pressure, and mean pulmonary artery pressure. Left ventricular pressure-volume loops showed that the slope of the end-systolic pressure-volume relation decreased markedly between the baseline and terminal study, suggesting a decrease in contractility. Echocardiographic studies indicated a decrease in ejection fraction. Histopathologic analysis in cardiac tissue showed extensive fibrosis and necrosis. CONCLUSION: We demonstrated the feasibility of inducing and maintaining severe yet stable heart failure for up to 3 weeks in a calf model by administration of oral monensin.