Biomedical subjects

H B Bittner

Publications and source records attributed to H B Bittner.

At least 37 records · Page 2Linked to original sources

PubMed1997

Right ventricular adaptation to increased afterload after orthotopic cardiac transplantation in the setting of recipient chronic pulmonary hypertension.

BACKGROUND: Right ventricular (RV) failure remains an important risk factor for early morbidity and mortality after orthotopic cardiac transplantation and is most commonly related to preexistent chronic pulmonary hypertension (CPH) in the recipient, which occurs secondary to long-standing congestive heart failure. This study was designed to assess the compensatory mechanisms of the acutely transplanted RV in the setting of recipient CPH using a canine model of bicaval cardiac transplantation (TX) and monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS: Twenty adult mongrel dogs were used for 10 successfully completed TX experiments. Recipients received an injection of 3 mg/kg MCTP 4 months before TX. RV function was assessed with load-insensitive means (preload recruitable stroke work), and Fourier analysis was used to calculate RV hydraulic power and transpulmonary efficiency. At the time of TX, significant increases in the mean pulmonary artery pressure, mean right ventricular pressure, and pulmonary vascular resistance were observed in recipients compared with donors and were further significantly increased after cardiopulmonary bypass. Significant increases in RV preload recruitable stroke work and RV hydraulic power were observed after TX compared with before TX and occurred in association with significant decreases in transpulmonary efficiency. CONCLUSIONS: Significant increases in pulmonary hemodynamic indexes occurred after MCTP injection and were further significantly increased after cardiopulmonary bypass. In the setting of recipient CPH, RV performance adapts acutely after bicaval TX with significant increases in power and contractility. However, a significant decrease in transpulmonary efficiency was also observed, which may improve over time as the RV adapts to the increased afterload.

Adaptation, Physiological↗

PubMed1997

Right ventricular failure--insights provided by a new model of chronic pulmonary hypertension.

This study was designed to examine the effects of both nitric oxide and milrinone on pulmonary hemodynamics and right ventricular function using a newly established model of monocrotaline pyrrole-induced chronic pulmonary hypertension. Sixteen mongrel dogs (23-25 kg) were used. All animals underwent percutanous pulmonary artery catheterization to measure right heart hemodynamics prior to and 8 weeks after a right atrial injection of either monocrotaline pyrrole (MCTP, n=8) or placebo (CTL, n=8). Eight weeks postinjection, all hearts were instrumented with a pulmonary artery flow probe and intracavitary micromanometers. Data were collected at baseline as well as following both nitric oxide and milrinone administration. There was no significant difference in the baseline hemodynamic measurements between the two groups. Eight weeks postinjection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed in MCTP compared with CTL. Both nitric oxide and milrinone resulted in significant improvements in pulmonary vascular resistance, pulmonary blood flow, and right ventricular contractility. In addition, nitric oxide caused a significant improvement in pulmonary artery pressure and transpulmonary efficiency, while milrinone led to a significant increase in right ventricular hydraulic power. This study demonstrates the well-known clinical effects of nitric oxide and milrinone in improving pulmonary hypertension, which were also associated with an increase in pulmonary blood flow, transpulmonary efficiency, and right ventricular hydraulic power in the setting of monocrotaline pyrrole-induced chronic pulmonary hypertension.

Administration, Inhalation↗

PubMed1997

Functional analysis of myocardial performance in murine hearts overexpressing the human beta 2-adrenergic receptor.

Transgenic mice overexpressing the human beta 2-adrenergic receptor gene were compared with wild mice type in terms of cardiac function, using a modified work-performing isolated murine heart preparation and on-line computer analysis. A preload-dependent experiment was performed, in which venous return was gradually increased in 5 mmHg increments from 5 mmHg to 25 mmHg. At each preload, aortic flow, left atrial pressure and aortic pressure were measured in all hearts, and from these parameters stroke volume, contractility, and cardiac index (cardiac output divided by body weight in g) were calculated and compared between groups. At increasing preload levels, the heart rates ranged from 322 beats/min (+/-29) to 369 beats/min (+/-39) in control mice and from 469 beats/min (+/-36) to 540 beats/min (+/-39) in transgenic mice. Cardiac index increased from 138 microliters/min/g (+/-13) and 48 microliters/min/g (+/-5) for transgenic and control mice, respectively at 5 mmHg preload to 262 microliters/min/g (+/-51) and 167 microliters/min/g (+/-15), respectively at 20 mmHg preload. The contractility in the transgenic mice were significantly increased at lower preload levels compared to control mice (1420 mmHg/s +/- 204 v 1187 mmHg/s +/- 127). An increase in myocardial adrenergic receptor density (100-200 fold) leads to significantly higher indices of cardiac function in transgenic mice compared to control mice. The increased heart rate leading to a positive inotropic effect in the hearts of transgenic mice is, at least in part, due to the overexpression of adrenergic receptors. These findings suggest a possible alternative method of establishing a positive chronotropic and inotropic state without the use of pharmacological agents.

Animals↗

PubMed1997

Hemodynamic and inotropic effects of nitric oxide in pulmonary hypertension.

Right ventricular failure following cardiac transplantation is most commonly related to pre-existent recipient pulmonary hypertension secondary to chronic congestive heart failure. Although nitric oxide has had some role clinically in improving pulmonary hemodynamics and right ventricular function in this setting, an appropriate large-animal model of stable pulmonary hypertension has not been available for basic investigation of this problem. This study was designed to examine the hemodynamic and inotropic effects of inhaled nitric oxide using a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. Eight mongrel dogs (22-25 kg) were used. All animals underwent percutaneous pulmonary artery catheterization to measure right heart hemodynamics prior to and 8 weeks after a right atrial injection of monocrotaline pyrrole. Eight weeks post-injection, all hearts were instrumented with a pulmonary artery flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and following nitric oxide administration. Eight weeks post-monocrotaline pyrrole injection, significant increases were observed in the pulmonary hemodynamics compared to pre-injection. Nitric oxide led to significant decreases in pulmonary vascular impedance. Significant improvements in pulmonary blood flow, transpulmonary efficiency, and right ventricular contractility were also observed. This investigation demonstrates the well-known clinical effects of nitric oxide in improving pulmonary hemodynamics which were also associated with an increase in pulmonary blood flow, transpulmonary efficiency, and right ventricular contractility in the setting of monocrotaline pyrrole-induced pulmonary hypertension.

Animals↗

PubMed1997

Pulmonary hemodynamics and blood flow characteristics in chronic pulmonary hypertension.

BACKGROUND: Lung transplantation is now an acceptable form of therapy for pulmonary hypertension, but controversy remains regarding the most appropriate surgical procedure. In this study, the changes in pulmonary vascular mechanics occurring in the setting of pulmonary hypertension were investigated using an adult canine model of monocrotaline pyrrole-induced pulmonary hypertension. METHODS: Animals underwent pulmonary artery catheterization to measure right heart pressures before and 8 weeks after injection of either 3 mg/kg of monocrotaline pyrrole (n = 8) or placebo (n = 8). Eight weeks after injection, hearts underwent instrumentation with an ultrasonic flow probe and micromanometers. Harmonic derivation of functional data was achieved with Fourier analysis. RESULTS: Significant increases in mean pulmonary artery pressure and pulmonary vascular resistance were observed after monocrotaline pyrrole injection. There was no significant difference in pulmonary blood flow. However, significant increases in input resistance and right ventricular hydraulic power with significant decreases in transpulmonary efficiency were observed. CONCLUSIONS: Pulmonary hypertension causes significant alterations in pulmonary hemodynamics. Pulmonary blood flow is maintained by a significant increase in total power but with a significant decrease in transpulmonary efficiency. This adult canine model of pulmonary hypertension provides a useful means by which to evaluate surgical options of lung transplantation for improving pulmonary hemodynamics in the setting of chronic pulmonary hypertension.

Animals↗

PubMed1997

Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension.

BACKGROUND: Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS: Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS: Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS: This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.

Animals↗

PubMed1997

Nitric oxide improves pulmonary vascular impedance, transpulmonary efficiency, and left ventricular filling in chronic pulmonary hypertension.

OBJECTIVE: Chronic pulmonary hypertension is difficult to treat and despite the introduction of several therapeutic options, no single therapy is universally recommended. Nitric oxide has had some role clinically in improving pulmonary hemodynamics in this setting; however, basic investigation has not been performed in an appropriate large animal model of stable pulmonary hypertension. This study was designed to examine the effects of inhaled nitric oxide on pulmonary hemodynamics in the setting of a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension and used Fourier analysis for assessment of pulmonary vascular impedance. METHODS: Sixteen mongrel dogs (22 to 25 kg) were used. Animals underwent percutaneous pulmonary artery catheterization to measure-right-sided hemodynamics before and 6 weeks after a right atrial injection of either monocrotaline pyrrole (n = 8) or placebo (n = 8). Six weeks after the injection all hearts were instrumented with an ultrasonic flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after nitric oxide administration. Harmonic derivation of functional data was achieved with Fourier analysis. RESULTS: Six weeks after the injection, significant increases in pulmonary artery pressure and pulmonary vascular resistance were observed in the monocrotaline pyrrole group. Nitric oxide led to significant decreases in pulmonary vascular impedance. Significant improvements in pulmonary blood flow, transpulmonary efficiency, and left ventricular filling were also observed. CONCLUSIONS: This investigation demonstrates the well-known clinical effects of nitric oxide in improving pulmonary hypertension, which were also associated with an increase in pulmonary blood flow, transpulmonary efficiency, and left ventricular filling in the setting of monocrotaline pyrrole-induced pulmonary hypertension.

Animals↗

PubMed1997

Right ventricular function in the donor heart.

OBJECTIVES: Early morbidity and mortality post cardiac transplantation is frequently caused by right ventricular failure; this is usually attributed to an elevated pulmonary vascular resistance in the recipient. Brain death in the donor is recognised as causing left ventricular dysfunction, but its effects on the right ventricle have not previously been studied. The aim of this study was to investigate right ventricular function following brain death, using a canine model. METHODS: The hearts of 33 dogs were instrumented with micromanometers, flow probes and dimension transducers to measure minor/major axes, and right and left ventricular free wall to septal distances. Left ventricular volume was calculated according to the prolate ellipsoid model and right ventricular volume was calculated according to the shell subtraction method. Systolic function for left and right ventricles was analysed by plotting ventricular stroke work vs. end-diastolic volume during a caval occlusion (preload-independent recruitable stroke work PRSW). Brain death was instigated by inflation of a subdurally placed intracranial balloon; subsequently blood pressure was maintained with intravenous fluid whilst no inotropic medications were given. Data were collected at baseline, and at 2 and 4 h thereafter. A two-tailed paired Student's t-test was applied to compare post-brain death data with baseline measurements. RESULTS: All animals had an initial hyperdynamic response post brain death ensued by the development of diabetes insipidus. Brain stem death was validated by neuropathological examination at the termination of the experiments. Right and left ventricular systolic function had deteriorated significantly 2 h post brain death by 34.4% (+/- 5.1%, P < 0.001) and 20.4% (+/- 3.4%, P < 0.001), respectively, from baseline PRSW [RV = 23.6 erg.10(3) (+/- 1.5), LV = 76.2 erg.10(3) (+/- 3.5)]. This deterioration remained at 4 h post brain death (29.4% (+/- 4.9%, P < 0.001) and 21.2% (+/- 4.3%, P < 0.001), respectively). (The results are expressed as mean and S.E.M.). CONCLUSIONS: Brain death causes a significant decrease in left and right ventricular function. The injury to the right ventricle is more prominent than the left ventricle, and at 2 h post brain death it is significantly greater. Failure of the right ventricle post transplantation in clinical practice may be related to this brain death induced injury. Further studies are required to investigate the mechanisms of this injury.

Animals↗

PubMed1997

Brain death alters cardiopulmonary hemodynamics and impairs right ventricular power reserve against an elevation of pulmonary vascular resistance.

Right ventricular (RV) failure, which is a leading cause of early morbidity and mortality following cardiac transplantation, is attributed to the inability of the donor RV to acutely compensate for the recipient's elevated pulmonary vascular resistance (PVR). Furthermore, the effect of donor brain death (BD) on RV function is unclear. The purpose of this study was to investigate the effects of donor BD on RV function in the setting of elevated PVR. The interactions of the RV and its afterload, the pulmonary vasculature, and left atrial pressure were assessed by measurements of pulmonary vascular energetics and their oscillatory nature using proximal ultrasonic pulmonary artery (PA) flow probe and micromanometers in the proximal and distal PA in 20 mongrel dogs (25.8 +/- 0.4 kg, five control animals). A band was placed around the distal PA (PA-systolic gradient > 15 mm Hg). BD was induced by rising intracranial pressure and was validated neuropathologically. Data were collected at 0, 2, 4, and 6 h after BD in both banded and control animals. Fourier analysis was used to calculate RV oscillatory power, mean power, and total power (TP). Comparison of changes due to banding were made to baseline measurements using multivariate analysis and paired Student's t test (p < 0.05). A significant twofold to fourfold increase in pulmonary impedance and PVR occurred with an acute rise in PA gradient. Control animals tolerated acute increases in PVR without significant changes in TP. There was a significant increase of RV TP from 73 (+/-11) to 98 (+/-10) mW at baseline after the acute rise in PVR and impedance. After BD, the response to increased PVR and impedance was abolished significantly compared with baseline and control animals, suggesting a significant loss of compensatory TP to sustain pulmonary vascular blood flow. The data indicate that BD is detrimental to RV mechanical function.

Animals↗

PubMed1997

Pulmonary vascular impedance and recipient chronic pulmonary hypertension following cardiac transplantation.

STUDY OBJECTIVES: Recipient chronic pulmonary hypertension (CPH), secondary to long-standing congestive heart failure, represents a significant risk factor for right ventricular (RV) dysfunction following orthotopic cardiac transplantation (TX). This study was designed to characterize the changes occurring in pulmonary hemodynamics, pre-TX and post-TX, using Fourier analysis, a canine model of bicaval TX, and monocrotaline pyrrole (MCTP)-induced recipient CPH. DESIGN: Prospective, controlled study. SETTING: Experimental laboratory. PARTICIPANTS: Twenty adult male mongrel dogs (23 to 26 kg). INTERVENTIONS: Recipients underwent pulmonary artery injection of 3 mg/kg MCTP 4 months pre-TX. On the day of TX, donor hearts were instrumented with an ultrasonic flow probe and micromanometers. Harmonic derivation of functional data was achieved with Fourier analysis. MEASUREMENTS AND RESULTS: At the time of TX, significant increases were observed in the mean pulmonary artery pressure and pulmonary vascular resistance of recipient animals in comparison to donors, which were further significantly increased following the termination of cardiopulmonary bypass. Significant increases were also observed in the input resistance, characteristic impedance, and RV hydraulic power post-TX compared to pre-TX, and occurred in association with a significant decrease in the transpulmonary efficiency. CONCLUSIONS: In the setting of MCTP-induced recipient CPH donor hearts were exposed to significant alterations in cardiopulmonary hemodynamics following bicaval TX. Pulmonary blood flow is maintained by a significantly higher energy expenditure by the RV, but at a lower level of efficiency. This experimental model may provide a useful means by which to evaluate therapeutic options to better manage cardiopulmonary hemodynamics in order to prevent RV failure following TX in the setting of recipient CPH.

Animals↗

PubMed1997

An adult canine model of chronic pulmonary hypertension for cardiopulmonary transplantation.

BACKGROUND: This study establishes a chemically-induced canine model of chronic pulmonary hypertension (CPH) using monocrotaline pyrrole (MCTP) and then characterizes this model in terms of hemodynamic, morphologic, and cardiac functional changes. METHODS: Thirty-three adult mongrel dogs (22 to 25 kg) were used. All animals underwent pulmonary artery catheterization to measure central venous pressure, mean right ventricular pressure (mRVP), mean pulmonary artery pressure (mPAP), and pulmonary capillary wedge pressure before and 6 weeks after a right atrial injection of either 60 mg/kg monocrotaline (group A, n = 8), 5 mg/kg MCTP (group B, n = 4), 3 mg/kg MCTP (group C, n = 13) or placebo (control, n = 8). Six weeks after injection, hearts in control and group C dogs were instrumented with flow probes, dimension transducers, and micromanometers to measure dynamic ventricular pressures and volumes. RESULTS: No significant differences in baseline hemodynamic indexes were observed between groups. All animals in group B and five in group C died after MCTP injection as a result of pulmonary edema. No significant increase in any hemodynamic parameters occurred in group A or in control dogs 6 weeks after injection. In group C, significant increases in central venous pressure, mRVP, and mPAP were observed 6 weeks after injection. Significant increases in right ventricular (RV) function and the weight ratio of the RV to left ventricle were observed in group C when compared with controls. CONCLUSIONS: A chemically-induced canine model of CPH has been created. Significant increases in mRVP, mPAP, and pulmonary capillary wedge pressure were observed 6 weeks after MCTP injection. RV function adapts to the increased afterload in the short term without evidence of failure. A stable model of pulmonary hypertension is provided as a potential means to evaluate posttransplantation RV dysfunction in the setting of CPH.

Age Factors↗

PubMed1997

Effects of nitric oxide after cardiac transplantation in the setting of recipient pulmonary hypertension.

BACKGROUND: Recipient pulmonary hypertension secondary to chronic congestive heart failure is a significant risk factor for right ventricular failure after cardiac transplantation. In this study, the hemodynamic and inotropic effects of nitric oxide (NO) were examined after bicaval cardiac transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension. METHODS: Twenty dogs underwent 10 successfully completed transplantation experiments. Recipients underwent pulmonary artery injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Measurements were taken 1 hour after cessation of cardiopulmonary bypass and after NO inhalation. Pulmonary vascular impedance was calculated using Fourier analysis, and cardiac function was assessed with load-insensitive means (preload recruitable stroke work). RESULTS: At the time of transplantation, the precardiopulmonary bypass levels of pulmonary vascular resistance in recipient animals were significantly greater when compared with donor levels, and were further significantly increased after cardiopulmonary bypass. Three recipients died after transplantation secondary to acute right ventricular failure. In the surviving animals, NO led to significant improvements in pulmonary vascular resistance and vascular impedance, which occurred in association with significant increases in transpulmonary efficiency. No significant changes were observed in right and left ventricular preload recruitable stroke work after NO inhalation. CONCLUSIONS: These data suggest that NO may be an effective means to improve vascular impedance and pulmonary vascular efficiency after cardiac transplantation in the setting of recipient chronic pulmonary hypertension.

Animals↗

PubMed1996

Total atrioventricular cardiac transplantation preserves atrial systole and ventricular diastolic filling.

BACKGROUND: Total orthotopic heart transplantation was recently introduced into clinical practice as an alternative technique for orthotopic cardiac transplantation. Total cardiac transplantation uses separate bicaval and left and right pulmonary anastomoses, whereas the standard technique of cardiac transplantation uses atrioplasty. Because the anatomic differences between total and standard orthotopic heart transplantation occur at the atrial level, this study compares atrial systolic function and biventricular filling (dV/dt) between the standard and total transplantation techniques. METHODS AND RESULTS: Forty-eight mongrel canines (23 to 31 kg) were used for 12 total and 12 standard orthotopic cardiac transplantations. Right and left ventricular (RV/LV) function and AV synchrony were analyzed with micromanometry, sonomicrometry, ultrasonic flow meters, and intraoperative echocardiography. Results are expressed as mean +/- SEM (ANOVA, paired and unpaired t tests, and chi 2 test). There were no significant differences in baseline function (pretransplantation), bypass times, and cardiac ischemic times between the two groups. Posttransplantation sinus rhythm was preserved in all total (P < 0025) and in only one standard transplantation recipient (all required atrial diastole pacing). Significant decreases in RV/LV dV/dt from 113 +/- 13 and 123 +/- 14 mL/s to 69 +/- 6 and 85 +/- 10 mL/s after transplantation were measured in the standard group. No significant changes occurred in the total group after transplantation with respect to RV/LV diastolic filling. After transplantation, left atrial contractility and relaxation (-dP/dt) decreased significantly in the standard group by 43% and 70%, respectively, whereas in the total transplantation group, there were no observed changes in left atrial contractility and-dP/dt. A significant increase in the septum to RV free wall dimension in the standard group suggests altered geometry. CONCLUSIONS: Total AV transplantation is a feasible alternative to standard cardiac transplantation and conserves both normal sinus rhythm and synchronized beating of the atria and ventricles. Ischemic and bypass times are comparable in patients undergoing either method. These data suggest that RV/LV diastolic function and geometry and atrial systole are better preserved in the total AV transplantation technique.

Animals↗

PubMed1996

Preload-recruitable stroke work relationships and diastolic dysfunction in the brain-dead organ donor.

BACKGROUND: Acute graft failure is an important cause of morbidity and mortality in cardiac transplantation, and it may be associated with myocardial changes that occur during brain death (BD). This study investigates the changes in biventricular systolic and diastolic function that occur after BD in a validated canine model. METHODS AND RESULTS: The hearts of 20 mongrel canines (23 to 31 kg) were instrumented with micromanometers, flow probes, and dimension transducers to measure minor/major axes as well as left and right ventricular (LV/RV) septum-to-free wall distances. LV/RV volumes were measured according to the shell subtraction method. LV/RV systolic function was analyzed by ventricular stroke work plotted versus end-diastolic volume during a caval occlusion (preload-independent recruitable systolic work, PRSW). The nonlinear relationships between diastatic pressure (stress) and LV/RV septum-to-free wall distances and volumes (strain) from successive diastoles during caval occlusion were used to evaluate LV/RV diastolic mechanics. The Cushing phenomenon, hyperdynamic response, and diabetes insipidus were observed in each animal after BD. Results are expressed as mean +/- SEM (P < .05 versus baseline, ANOVA, paired two-tailed Student's t test). Biventricular systolic function deteriorated significantly from baseline PRSW 6 to 7 hours after BD. The diastatic LV/RV pressure dimension relationships were significantly different after BD, indicating a decrease in ventricular chamber compliance during diastole. CONCLUSIONS: BD causes a significant loss of systolic and diastolic LV/RV function in the brain-dead, heart-beating cadaver, which may contribute to early postoperative cardiac graft failure in the recipient. These findings have significant clinical applications and may help to avoid suboptimal donor/recipient matches.

Animals↗

PubMed1996

Extracellular superoxide dismutase transgene overexpression preserves postischemic myocardial function in isolated murine hearts.

BACKGROUND: Myocardial injury after ischemia and reperfusion may be mediated, at least in part, by oxygen-derived free radicals; this supposition is supported by the observation that significant quantities of these radicals are generated during reperfusion. To directly assess the protective effect of extracellular superoxide dismutase (EC-SOD), this study was designed to investigate the ability of EC-SOD overexpression in the hearts of transgenic mice to protect myocardial tissue against ischemiareperfusion injury by use of an isolated work performing murine heart preparation and functional analysis. METHODS AND RESULTS: Ten transgenic mice (EC.SOD, 28 to 31 g) were studied and compared with 10 control mice (Ctl, 28 to 31 g) in terms of preischemic and postischemic myocardial function. All hearts underwent cardiac harvest and arrest, followed by instrumentation and subsequent reperfusion with warm Krebs-Henseleit solution. Preload-dependent functional analysis was then performed to evaluate cardiac output, contractility (dP/dt), heart rate, stroke work, and stroke volume before and after a 7-minute period of warm ischemia. Results are expressed as mean +/- SEM (ANOVA, paired unpaired t tests). There was no significant difference in preischemic myocardial performance for Ctl and EC-SOD mice. After warm ischemia, cardiac output in EC-SOD was significantly improved compared with Ctl (EC-SOD, 4.55 +/- 0.37 mL/min; Ctl, 2.55 +/- 0.28 mL/min; P < .05). Postischemic dP/dt, stroke work, and stroke volume were also significantly improved in EC-SOD compared with Ctl mice (EC-SOD, 1808 +/- 39 mm Hg/s, 745 +/- 67 dyne.cm, and 13.1 +/- 1.2 microL, respectively; Ctl, 1497 +/- 87 mm Hg/s, 472 +/- 83 dyne.cm, and 8.2 +/- 1.5 microL; P < .05). CONCLUSIONS: EC-SOD overexpressed mice showed significant improvement in postischemic cardiac function compared with Ctl mice. Thus, EC-SOD overexpressed hearts are less susceptible to mild degrees of ischemia-reperfusion injury than normal hearts.

Animals↗

PubMed1996

A work-performing heart preparation for myocardial performance analysis in murine hearts.

UNLABELLED: The mouse has become the animal of choice for genetic manipulations resulting in altered myocardial function, but assessment of cardiac function is extremely difficult due to the animal's size. This study was designed to establish a work-performing isolated mouse heart preparation to objectively investigate myocardial performance in murine hearts. Isolated work-performing cardiac functional studies were performed on a modified Langendorff apparatus using 15 mice [25 to 28 g, +/-0.4 (SEM)]. The hearts were instrumented with a transonic flow meter and micromanometers to measure on-line aortic flow (AF), aortic pressure, and left atrial pressure (preload). A VAX cardiac function analyzing system was used to determine cardiac parameters including heart rate, contractility (max dP/dt), stroke volume (SV), and stroke work (SW) at various preload levels compared to a baseline preload of 5 mm Hg before and after 7 min of warm ischemia. AF increased from 1.01 ml/min (+/- 0.26) at 5 mm Hg of preload to 4.15 ml/min (+/- 1.03, P < 0.05) at 20 mm Hg of preload and decreased to 3.64 ml/min (+/- 0.62) at 25 mm Hg. SV, dP/dt, and SW increased with higher preload levels. There was a significant decrease in cardiac function postischemia. CONCLUSIONS: A valid isolated work-performing preload-dependent murine heart preparation involving minimal instrumentation of the heart is established to measure cardiac function and myocardial performance. Significant ischemia-reperfusion injury occurred after 7 min of ischemia. This model is a reliable and objective tool by which to evaluate murine cardiac function and to study ischemia-reperfusion injury.

Animals↗

PubMed1996

Brain death further promotes ischemic reperfusion injury of the rabbit myocardium.

BACKGROUND: Little is known about preload-dependent cardiac function after brain death (BD) and subsequent graft preservation. METHODS: A validated model of BD in rabbits was developed and myocardial performance was studied after BD induction and 1 hour of subsequent global hypothermic ischemia using a validated rabbit model and an isolated work-performing heart preparation. RESULTS: Significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed 2 hours after BD. After global hypothermic ischemia, significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed in the BD group compared with controls. Cardiac output and coronary flow were also significantly decreased in BD hearts compared with controls. Creatine kinase release was increased by 32.5% in BD hearts compared with controls. CONCLUSIONS: In a rabbit model, BD combined with global hypothermic ischemia causes a significant decrease in left ventricular function compared with global hypothermic ischemia. This dysfunction may be attributed to a significant decrease in coronary flows in BD hearts.

Animals↗

PubMed1996

Nitric oxide in brain death related cardiovascular dysfunction.

PURPOSE: Nitric oxide (NO) is a major regulator of vascular tone, blood pressure, and blood flow, and plays a significant role in disease states associated with hemodynamic alterations. However, the role of NO in association with the effects of brain death (BD) has not yet been evaluated. METHODS: In 17 mongrel dogs (23 to 31 kg), right atrial serum measurements of nitrite and L-arginine as well as NO ex vivo tissue nitrite extraction were performed at baseline (0), and 120, 240, and 360 minutes after BD. The hearts were instrumented with micromanometers, transonic flow probes, and ultrasonic dimension transducers to determine systolic function and to analyze the pulmonary vasculature flow characteristics by Fourier analysis. Brain death was induced by inflation of a subdurally placed balloon and validated neuropathologically. The results are expressed as mean and standard error of the mean (+/- SEM) (P < .05, paired t-test). RESULTS: Right and left ventricular function deteriorated significantly (P < .001) by 37% (+/- 10) and 22% (+/- 7) respectively following BD. Pulmonary and systemic vascular resistance as well as pulmonary impedance decreased significantly over 6 hours after BD. Pulsatile flow, a potent stimulant of NO release, converted significantly to more steady flow. Myocardial NO extraction values remained unchanged after BD and serum L-arginine decreased from 12.84 mu g/L (+/- 0.60) to 11.77 mu g/L (+/- 0.55). CONCLUSIONS: The decreases in pulmonary and systemic vascular resistance, pulmonary impedance, and cardiac function associated with BD are not related to major changes in the NO pathway. NO may not play a key role in the early changes after BD.

Animals↗