Toxic effects, pharmacokinetics and clearanceof saxitoxin, a component of paralytic shellfishpoison (PSP), in cats

2.ANDRINOLO, D., MICHEA, L.F., & LAGOS, N

TOXICON

Año: 1999 vol. 37 p. 447 - 464

0041-0101

Saxitoxin (STX) was the ®rst known and most studied toxic component of paralytic shell®sh poisoning (PSP). This toxin blocks neuronal transmission by binding to the voltage-gated Na+ channel. Although the toxin´s mechanism of action is well known at the molecular level, there are still many unresolved questions about its pharmacokinetics and the PSP intoxication syndrome in mammals. Some of these questions are addressed in the present paper, which describes an experimental design which allowed us to follow the dynamics of STX poisoning in vivo. Adult cats were anaesthetized and permanently coupled to arti®cial ventilation, they were then intravenously injected with Low (2.7 mg of STX/kg) and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters to arti®cial ventilation, they were then intravenously injected with Low (2.7 mg of STX/kg) and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the molecular level, there are still many unresolved questions about its pharmacokinetics and the PSP intoxication syndrome in mammals. Some of these questions are addressed in the present paper, which describes an experimental design which allowed us to follow the dynamics of STX poisoning in vivo. Adult cats were anaesthetized and permanently coupled to arti®cial ventilation, they were then intravenously injected with Low (2.7 mg of STX/kg) and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters to arti®cial ventilation, they were then intravenously injected with Low (2.7 mg of STX/kg) and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters and high doses (10 mg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters pressure and electrocardiograms were recorded, urine and blood samples were collected during the four hours of experimental time. In order to quantify mass amount of STX, we used the post-column derivatization HPLC method. Urine and blood samples were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge ®lters. At the end of each experiment, the animals were killed and tissue samples from brain, liver, spleen and medulla oblongata were extracted to measure the amount of STX. As compared to control period, Low doses of STX made no di€erence in hemodynamics parameters. In contrast, high doses drastically reduced blood pressure, produced myocardial failure and ®nally cardiac arrest. Administration of 2.5 mg/kgmin of dobutamine restored hemodynamics parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters parameters and allowed the animal to overcome the shock. With high doses, the calculated STX renal clearance in cats is 0.81 ml/minkgÿ1. This valued corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with Low doses the STX renal clearance is 3.99 ml/minkgÿ1. This data suggest that in cats with normal cardiovascular parameters