The Experts below are selected from a list of 612 Experts worldwide ranked by ideXlab platform
Joseph Winaver - One of the best experts on this subject based on the ideXlab platform.
-
Aortocaval Fistula in rat a unique model of volume overload congestive heart failure and cardiac hypertrophy
BioMed Research International, 2011Co-Authors: Zaid Abassi, Joseph Winaver, Ilia Goltsman, Tony Karram, Aaron HoffmanAbstract:Despite continuous progress in our understanding of the pathogenesis of congestive heart failure (CHF) and its management, mortality remains high. Therefore, development of reliable experimental models of CHF and cardiac hypertrophy is essential to better understand disease progression and allow new therapy developement. The Aortocaval Fistula (ACF) model, first described in dogs almost a century ago, has been adopted in rodents by several groups including ours. Although considered to be a model of high-output heart failure, its long-term renal and cardiac manifestations are similar to those seen in patients with low-output CHF. These include Na+-retention, cardiac hypertrophy and increased activity of both vasoconstrictor/antinatriureticneurohormonal systems and compensatory vasodilating/natriuretic systems. Previous data from our group and others suggest that progression of cardiorenal pathophysiology in this model is largely determined by balance between opposing hormonal forces, as reflected in states of CHF decompensation that are characterized by overactivation of vasoconstrictive/Na+-retaining systems. Thus, ACF serves as a simple, cheap, and reproducible platform to investigate the pathogenesis of CHF and to examine efficacy of new therapeutic approaches. Hereby, we will focus on the neurohormonal, renal, and cardiac manifestations of the ACF model in rats, with special emphasis on our own experience.
-
role of myocardial inducible nitric oxide synthase in contractile dysfunction and β adrenergic hyporesponsiveness in rats with experimental volume overload heart failure
Circulation, 2002Co-Authors: Olga Gealekman, Joseph Winaver, Zaid Abassi, Irit Rubinstein, Ofer BinahAbstract:Background— Whereas nitric oxide (NO) has been implicated in the pathophysiology of heart failure (HF), the significance and functional role of different NO synthase (NOS) isoforms in this pathology are controversial. Our aim was to study in the myocardium of rats with volume-overload–induced HF the expression, activity, and localization of endothelial (eNOS) and inducible (iNOS) isoforms and the involvement of iNOS in depressed cardiac contractile properties, intracellular Ca2+ ([Ca2+]i) transients, and β-adrenergic hyporesponsiveness. Methods and Results— HF was induced by Aortocaval Fistula (ACF). Compensated and decompensated subgroups of HF were selected on the basis of daily sodium excretion. ACF induced cardiac hypertrophy in rats with compensated (36%) and decompensated (76%) HF. Whereas in HF rats, cardiac eNOS expression and activity were unchanged, iNOS expression and activity increased ≈2-fold. iNOS immunostaining was observed in ventricular myocytes of compensated and decompensated HF rats bu...
-
monocyte chemoattractant protein 1 is upregulated in rats with volume overload congestive heart failure
Circulation, 2000Co-Authors: Thomas M Behr, Giora Z Feuerstein, Xinkang Wang, Nambi Aiyar, Robert W Coatney, Xiang Li, Paul F Koster, Christiane E Angermann, Eliot H Ohlstein, Joseph WinaverAbstract:Background —Chemokines are potent proinflammatory and immune modulators. Increased expression of chemokines, eg, monocyte chemoattractant protein-1 (MCP-1), has recently been described in clinical and experimental heart failure. The present report is aimed at exploring the expression, localization, and binding site regulation of MCP-1, a member of the C-C chemokine family, in a rat model of volume-overload congestive heart failure (CHF). Methods and Results —An Aortocaval Fistula was surgically created between the abdominal aorta and inferior vena cava. Rats with CHF were further subdivided into compensated and decompensated subgroups. Northern blot analysis and real-time quantitative polymerase chain reaction demonstrated upregulation of MCP-1 mRNA expression correlating with the severity of CHF (288±22, 502±62, and 826±138 copies/ng total RNA for sham, compensated, and decompensated animals, respectively; n=5, P <0.05). MCP-1 protein was localized by immunohistochemistry in cardiomyocytes, vascular endothelium and smooth muscle cells, infiltrating leukocytes, and interstitial fibroblasts, and its intensity increased with severity of CHF. In addition, rats with CHF displayed a significant decrease of 125I-labeled MCP-1 binding sites to myocardium-derived membranes (384.3±57.0, 181.3±8.8, and 123.3±14.1 fmol/mg protein for sham, compensated, and decompensated animals, respectively). Conclusions —Volume-overload CHF in rats is associated with alterations in the expression, immunohistochemical localization, and receptor binding of the MCP-1 chemokine in the myocardium. These changes were more pronounced in rats with decompensated CHF. The data suggest that activation of the MCP-1 system may contribute to the progressive cardiac decompensation and development of CHF in rats with Aortocaval Fistula.
-
effects of eprosartan on renal function and cardiac hypertrophy in rats with experimental heart failure
Hypertension, 1998Co-Authors: Sergey Brodsky, Robert R. Ruffolo, Konstantin Gurbanov, Aaron Hoffman, Zaid Abassi, Giora Z Feuerstein, Joseph WinaverAbstract:Abstract —Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with Aortocaval Fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with Aortocaval Fistula produced a significant increase (+34%) in total renal blood flow and a sustained decrease (−33%) in the calculated renal vascular resistance. These effects on renal hemodynamics were more pronounced than those observed in sham-operated control rats and occurred despite a significant fall (−12%) in mean arterial blood pressure. Moreover, eprosartan caused a preferential increase in renal cortical blood perfusion and significantly increased glomerular filtration in rats with congestive heart failure. Chronic administration of eprosartan (5.0 mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on the day of operation) resulted in a significant enhancement of urinary sodium excretion compared with nontreated rats with heart failure. Moreover, administration of eprosartan to salt-retaining rats with congestive heart failure resulted in a progressive increase and ultimate recovery in urinary sodium excretion. Finally, early treatment with eprosartan blocked the development of cardiac hypertrophy in rats with Aortocaval Fistula to a larger extent than the angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the importance of angiotensin II in mediating the impairment in renal function and induction of cardiac hypertrophy in heart failure and further suggest that angiotensin II receptor blockade may be a useful treatment of these consequences in severe cardiac failure.
Zaid Abassi - One of the best experts on this subject based on the ideXlab platform.
-
Aortocaval Fistula in rat a unique model of volume overload congestive heart failure and cardiac hypertrophy
BioMed Research International, 2011Co-Authors: Zaid Abassi, Joseph Winaver, Ilia Goltsman, Tony Karram, Aaron HoffmanAbstract:Despite continuous progress in our understanding of the pathogenesis of congestive heart failure (CHF) and its management, mortality remains high. Therefore, development of reliable experimental models of CHF and cardiac hypertrophy is essential to better understand disease progression and allow new therapy developement. The Aortocaval Fistula (ACF) model, first described in dogs almost a century ago, has been adopted in rodents by several groups including ours. Although considered to be a model of high-output heart failure, its long-term renal and cardiac manifestations are similar to those seen in patients with low-output CHF. These include Na+-retention, cardiac hypertrophy and increased activity of both vasoconstrictor/antinatriureticneurohormonal systems and compensatory vasodilating/natriuretic systems. Previous data from our group and others suggest that progression of cardiorenal pathophysiology in this model is largely determined by balance between opposing hormonal forces, as reflected in states of CHF decompensation that are characterized by overactivation of vasoconstrictive/Na+-retaining systems. Thus, ACF serves as a simple, cheap, and reproducible platform to investigate the pathogenesis of CHF and to examine efficacy of new therapeutic approaches. Hereby, we will focus on the neurohormonal, renal, and cardiac manifestations of the ACF model in rats, with special emphasis on our own experience.
-
role of myocardial inducible nitric oxide synthase in contractile dysfunction and β adrenergic hyporesponsiveness in rats with experimental volume overload heart failure
Circulation, 2002Co-Authors: Olga Gealekman, Joseph Winaver, Zaid Abassi, Irit Rubinstein, Ofer BinahAbstract:Background— Whereas nitric oxide (NO) has been implicated in the pathophysiology of heart failure (HF), the significance and functional role of different NO synthase (NOS) isoforms in this pathology are controversial. Our aim was to study in the myocardium of rats with volume-overload–induced HF the expression, activity, and localization of endothelial (eNOS) and inducible (iNOS) isoforms and the involvement of iNOS in depressed cardiac contractile properties, intracellular Ca2+ ([Ca2+]i) transients, and β-adrenergic hyporesponsiveness. Methods and Results— HF was induced by Aortocaval Fistula (ACF). Compensated and decompensated subgroups of HF were selected on the basis of daily sodium excretion. ACF induced cardiac hypertrophy in rats with compensated (36%) and decompensated (76%) HF. Whereas in HF rats, cardiac eNOS expression and activity were unchanged, iNOS expression and activity increased ≈2-fold. iNOS immunostaining was observed in ventricular myocytes of compensated and decompensated HF rats bu...
-
effects of eprosartan on renal function and cardiac hypertrophy in rats with experimental heart failure
Hypertension, 1998Co-Authors: Sergey Brodsky, Robert R. Ruffolo, Konstantin Gurbanov, Aaron Hoffman, Zaid Abassi, Giora Z Feuerstein, Joseph WinaverAbstract:Abstract —Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with Aortocaval Fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with Aortocaval Fistula produced a significant increase (+34%) in total renal blood flow and a sustained decrease (−33%) in the calculated renal vascular resistance. These effects on renal hemodynamics were more pronounced than those observed in sham-operated control rats and occurred despite a significant fall (−12%) in mean arterial blood pressure. Moreover, eprosartan caused a preferential increase in renal cortical blood perfusion and significantly increased glomerular filtration in rats with congestive heart failure. Chronic administration of eprosartan (5.0 mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on the day of operation) resulted in a significant enhancement of urinary sodium excretion compared with nontreated rats with heart failure. Moreover, administration of eprosartan to salt-retaining rats with congestive heart failure resulted in a progressive increase and ultimate recovery in urinary sodium excretion. Finally, early treatment with eprosartan blocked the development of cardiac hypertrophy in rats with Aortocaval Fistula to a larger extent than the angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the importance of angiotensin II in mediating the impairment in renal function and induction of cardiac hypertrophy in heart failure and further suggest that angiotensin II receptor blockade may be a useful treatment of these consequences in severe cardiac failure.
-
expression of renin angiotensin system components in the heart kidneys and lungs of rats with experimental heart failure
Circulation, 1995Co-Authors: Federico Pieruzzi, Zaid Abassi, Harry R KeiserAbstract:Background Chronic activation of the renin-angiotensin system (RAS) plays an important role in the pathogenesis of heart failure. Increasing evidence indicates that other than the circulating RAS, a local RAS exists in several tissues, including the heart. The present study was carried out to quantify cardiac, renal, and pulmonary mRNA levels of renin, angiotensin-converting enzyme (ACE), and types 1 and 2 angiotensin II receptors (AT-1 and AT-2), in rats with different severities of heart failure. Methods and Results Heart failure was induced by the creation of an Aortocaval Fistula below the renal arteries. Rats with Aortocaval Fistula either compensate and maintain a normal sodium balance or decompensate and develop severe sodium retention. Six days after placement of the Aortocaval Fistula, heart weight (normalized to body weight) increased 35% (P<.05) in compensated and 65% in decompensated rats compared with control rats. Plasma renin activity increased 45% (P<.05) in rats in sodium balance and 127%...
Sascha Treskatsch - One of the best experts on this subject based on the ideXlab platform.
-
A Modified Approach to Induce Predictable Congestive Heart Failure by Volume Overload in Rats
2016Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Shaaban A Mousa, Adrian T. Rosin, Marco Sifringer, Helmut Habazettl, Claudia D. SpiesAbstract:The model of infrarenal Aortocaval Fistula (ACF) has recently gained new interest in its use to investigate cardiac pathophysiology. Since in previous investigations the development of congestive heart failure (CHF) was inconsistent and started to develop earliest 8–10 weeks after Fistula induction using a 18G needle, this project aimed to induce a predictable degree of CHF within a definite time period using a modified approach. An Aortocaval Fistula was induced in male Wistar rats using a 16G needle as a modification of the former 18G needle-technique described by Garcia and Diebold. Results revealed within 2862 days of ACF significantly increased heart and lung weight indices in the ACF group accompanied by elevated filling pressure. All hemodynamic parameters derived from a pressure-volume conductance-catheter in vivo were significantly altered in the ACF consistent with severe systolic and diastolic left ventricular dysfunction. This was accompanied by systemic neurohumoral activation as demonstrated by elevated rBNP-45 plasma concentrations in every rat of the ACF group. Furthermore, the restriction in overall cardiac function was associated with a b1- and b2-adrenoreceptor mRNA downregulation in the left ventricle. In contrast, b3-adrenoreceptor mRNA was upregulated. Finally, electron microscopy of the left ventricle of rats in the ACF group showed signs of progressive subcellular myocardial fragmentation. In conclusion, the morphometric, hemodynamic and neurohumoral characterization of the modified approach revealed predictable and consistent signs of congestive heart failure within 2862 days. Therefore, this modifie
-
ultrastructural changes associated with myocardial apoptosis in failing rat hearts induced by volume overload
International Journal of Cardiology, 2015Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Mohammed Shaqura, Lukas Dehe, Torsten K Roepke, Claudia Spies, Michael Schafer, Shaaban A MousaAbstract:Abstract Background Myocardial apoptosis has been discussed to play a pivotal role in the development and progression of congestive heart failure (CHF). However, recently there is doubt on the evidence of myocardial apoptosis in heart failure as information on ultrastructural changes by electron microscopy is still scarce. This project therefore aimed to detect direct morphological evidence of myocardial apoptosis in an experimental heart failure model. Method Following IRB approval, an Aortocaval Fistula (ACF) was induced in male Wistar rats using a 16G needle. 28±2days following ACF rats were examined by hemodynamic measurements, Western blot, immunofluorescence confocal and electron microscopic analysis. Results Within 28±2days of ACF heart (3.8±0.1 vs. 6.6±0.3mg/g) and lung (3.7±0.2 vs. 6.9±0.5mg/g) weight indices significantly increased in the ACF group accompanied by a restriction in systolic (LVEF: 72±2 vs. 39±3%) and diastolic (dP/dt min. : −10,435±942 vs. −5982±745mmHg/s) function (p 70% of examined cardiomyocytes, such as nuclear chromatin condensation, myofibril loss and disarray, contour irregularities and amorphous dense bodies, mitochondriosis and damaged cell–cell-contacts between cardiomyocytes. Conclusions Volume overload induced heart failure is associated with activation of the mitochondrial apoptotic pathway. In addition, electron microscopy of the LV revealed direct ultrastructural evidence of extended myocardial apoptosis in ACF rats.
-
a modified approach to induce predictable congestive heart failure by volume overload in rats
PLOS ONE, 2014Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Michael Schafer, Shaaban A Mousa, Adrian T. Rosin, Marco Sifringer, Helmut Habazettl, Claudia SpiesAbstract:The model of infrarenal Aortocaval Fistula (ACF) has recently gained new interest in its use to investigate cardiac pathophysiology. Since in previous investigations the development of congestive heart failure (CHF) was inconsistent and started to develop earliest 8–10 weeks after Fistula induction using a 18G needle, this project aimed to induce a predictable degree of CHF within a definite time period using a modified approach. An Aortocaval Fistula was induced in male Wistar rats using a 16G needle as a modification of the former 18G needle-technique described by Garcia and Diebold. Results revealed within 28±2 days of ACF significantly increased heart and lung weight indices in the ACF group accompanied by elevated filling pressure. All hemodynamic parameters derived from a pressure-volume conductance-catheter in vivo were significantly altered in the ACF consistent with severe systolic and diastolic left ventricular dysfunction. This was accompanied by systemic neurohumoral activation as demonstrated by elevated rBNP-45 plasma concentrations in every rat of the ACF group. Furthermore, the restriction in overall cardiac function was associated with a β1- and β2-adrenoreceptor mRNA downregulation in the left ventricle. In contrast, β3-adrenoreceptor mRNA was upregulated. Finally, electron microscopy of the left ventricle of rats in the ACF group showed signs of progressive subcellular myocardial fragmentation. In conclusion, the morphometric, hemodynamic and neurohumoral characterization of the modified approach revealed predictable and consistent signs of congestive heart failure within 28±2 days. Therefore, this modified approach might facilitate the examination of various questions specific to CHF and allow for pharmacological interventions to determine pathophysiological pathways.
Claudia Spies - One of the best experts on this subject based on the ideXlab platform.
-
ultrastructural changes associated with myocardial apoptosis in failing rat hearts induced by volume overload
International Journal of Cardiology, 2015Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Mohammed Shaqura, Lukas Dehe, Torsten K Roepke, Claudia Spies, Michael Schafer, Shaaban A MousaAbstract:Abstract Background Myocardial apoptosis has been discussed to play a pivotal role in the development and progression of congestive heart failure (CHF). However, recently there is doubt on the evidence of myocardial apoptosis in heart failure as information on ultrastructural changes by electron microscopy is still scarce. This project therefore aimed to detect direct morphological evidence of myocardial apoptosis in an experimental heart failure model. Method Following IRB approval, an Aortocaval Fistula (ACF) was induced in male Wistar rats using a 16G needle. 28±2days following ACF rats were examined by hemodynamic measurements, Western blot, immunofluorescence confocal and electron microscopic analysis. Results Within 28±2days of ACF heart (3.8±0.1 vs. 6.6±0.3mg/g) and lung (3.7±0.2 vs. 6.9±0.5mg/g) weight indices significantly increased in the ACF group accompanied by a restriction in systolic (LVEF: 72±2 vs. 39±3%) and diastolic (dP/dt min. : −10,435±942 vs. −5982±745mmHg/s) function (p 70% of examined cardiomyocytes, such as nuclear chromatin condensation, myofibril loss and disarray, contour irregularities and amorphous dense bodies, mitochondriosis and damaged cell–cell-contacts between cardiomyocytes. Conclusions Volume overload induced heart failure is associated with activation of the mitochondrial apoptotic pathway. In addition, electron microscopy of the LV revealed direct ultrastructural evidence of extended myocardial apoptosis in ACF rats.
-
a modified approach to induce predictable congestive heart failure by volume overload in rats
PLOS ONE, 2014Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Michael Schafer, Shaaban A Mousa, Adrian T. Rosin, Marco Sifringer, Helmut Habazettl, Claudia SpiesAbstract:The model of infrarenal Aortocaval Fistula (ACF) has recently gained new interest in its use to investigate cardiac pathophysiology. Since in previous investigations the development of congestive heart failure (CHF) was inconsistent and started to develop earliest 8–10 weeks after Fistula induction using a 18G needle, this project aimed to induce a predictable degree of CHF within a definite time period using a modified approach. An Aortocaval Fistula was induced in male Wistar rats using a 16G needle as a modification of the former 18G needle-technique described by Garcia and Diebold. Results revealed within 28±2 days of ACF significantly increased heart and lung weight indices in the ACF group accompanied by elevated filling pressure. All hemodynamic parameters derived from a pressure-volume conductance-catheter in vivo were significantly altered in the ACF consistent with severe systolic and diastolic left ventricular dysfunction. This was accompanied by systemic neurohumoral activation as demonstrated by elevated rBNP-45 plasma concentrations in every rat of the ACF group. Furthermore, the restriction in overall cardiac function was associated with a β1- and β2-adrenoreceptor mRNA downregulation in the left ventricle. In contrast, β3-adrenoreceptor mRNA was upregulated. Finally, electron microscopy of the left ventricle of rats in the ACF group showed signs of progressive subcellular myocardial fragmentation. In conclusion, the morphometric, hemodynamic and neurohumoral characterization of the modified approach revealed predictable and consistent signs of congestive heart failure within 28±2 days. Therefore, this modified approach might facilitate the examination of various questions specific to CHF and allow for pharmacological interventions to determine pathophysiological pathways.
Shaaban A Mousa - One of the best experts on this subject based on the ideXlab platform.
-
A Modified Approach to Induce Predictable Congestive Heart Failure by Volume Overload in Rats
2016Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Shaaban A Mousa, Adrian T. Rosin, Marco Sifringer, Helmut Habazettl, Claudia D. SpiesAbstract:The model of infrarenal Aortocaval Fistula (ACF) has recently gained new interest in its use to investigate cardiac pathophysiology. Since in previous investigations the development of congestive heart failure (CHF) was inconsistent and started to develop earliest 8–10 weeks after Fistula induction using a 18G needle, this project aimed to induce a predictable degree of CHF within a definite time period using a modified approach. An Aortocaval Fistula was induced in male Wistar rats using a 16G needle as a modification of the former 18G needle-technique described by Garcia and Diebold. Results revealed within 2862 days of ACF significantly increased heart and lung weight indices in the ACF group accompanied by elevated filling pressure. All hemodynamic parameters derived from a pressure-volume conductance-catheter in vivo were significantly altered in the ACF consistent with severe systolic and diastolic left ventricular dysfunction. This was accompanied by systemic neurohumoral activation as demonstrated by elevated rBNP-45 plasma concentrations in every rat of the ACF group. Furthermore, the restriction in overall cardiac function was associated with a b1- and b2-adrenoreceptor mRNA downregulation in the left ventricle. In contrast, b3-adrenoreceptor mRNA was upregulated. Finally, electron microscopy of the left ventricle of rats in the ACF group showed signs of progressive subcellular myocardial fragmentation. In conclusion, the morphometric, hemodynamic and neurohumoral characterization of the modified approach revealed predictable and consistent signs of congestive heart failure within 2862 days. Therefore, this modifie
-
ultrastructural changes associated with myocardial apoptosis in failing rat hearts induced by volume overload
International Journal of Cardiology, 2015Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Mohammed Shaqura, Lukas Dehe, Torsten K Roepke, Claudia Spies, Michael Schafer, Shaaban A MousaAbstract:Abstract Background Myocardial apoptosis has been discussed to play a pivotal role in the development and progression of congestive heart failure (CHF). However, recently there is doubt on the evidence of myocardial apoptosis in heart failure as information on ultrastructural changes by electron microscopy is still scarce. This project therefore aimed to detect direct morphological evidence of myocardial apoptosis in an experimental heart failure model. Method Following IRB approval, an Aortocaval Fistula (ACF) was induced in male Wistar rats using a 16G needle. 28±2days following ACF rats were examined by hemodynamic measurements, Western blot, immunofluorescence confocal and electron microscopic analysis. Results Within 28±2days of ACF heart (3.8±0.1 vs. 6.6±0.3mg/g) and lung (3.7±0.2 vs. 6.9±0.5mg/g) weight indices significantly increased in the ACF group accompanied by a restriction in systolic (LVEF: 72±2 vs. 39±3%) and diastolic (dP/dt min. : −10,435±942 vs. −5982±745mmHg/s) function (p 70% of examined cardiomyocytes, such as nuclear chromatin condensation, myofibril loss and disarray, contour irregularities and amorphous dense bodies, mitochondriosis and damaged cell–cell-contacts between cardiomyocytes. Conclusions Volume overload induced heart failure is associated with activation of the mitochondrial apoptotic pathway. In addition, electron microscopy of the LV revealed direct ultrastructural evidence of extended myocardial apoptosis in ACF rats.
-
a modified approach to induce predictable congestive heart failure by volume overload in rats
PLOS ONE, 2014Co-Authors: Sascha Treskatsch, Mehdi Shakibaei, Aarne Feldheiser, Michael Schafer, Shaaban A Mousa, Adrian T. Rosin, Marco Sifringer, Helmut Habazettl, Claudia SpiesAbstract:The model of infrarenal Aortocaval Fistula (ACF) has recently gained new interest in its use to investigate cardiac pathophysiology. Since in previous investigations the development of congestive heart failure (CHF) was inconsistent and started to develop earliest 8–10 weeks after Fistula induction using a 18G needle, this project aimed to induce a predictable degree of CHF within a definite time period using a modified approach. An Aortocaval Fistula was induced in male Wistar rats using a 16G needle as a modification of the former 18G needle-technique described by Garcia and Diebold. Results revealed within 28±2 days of ACF significantly increased heart and lung weight indices in the ACF group accompanied by elevated filling pressure. All hemodynamic parameters derived from a pressure-volume conductance-catheter in vivo were significantly altered in the ACF consistent with severe systolic and diastolic left ventricular dysfunction. This was accompanied by systemic neurohumoral activation as demonstrated by elevated rBNP-45 plasma concentrations in every rat of the ACF group. Furthermore, the restriction in overall cardiac function was associated with a β1- and β2-adrenoreceptor mRNA downregulation in the left ventricle. In contrast, β3-adrenoreceptor mRNA was upregulated. Finally, electron microscopy of the left ventricle of rats in the ACF group showed signs of progressive subcellular myocardial fragmentation. In conclusion, the morphometric, hemodynamic and neurohumoral characterization of the modified approach revealed predictable and consistent signs of congestive heart failure within 28±2 days. Therefore, this modified approach might facilitate the examination of various questions specific to CHF and allow for pharmacological interventions to determine pathophysiological pathways.