Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.

Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.

Saline infusion volume/rate matched to the calculated dose of esmolol.

Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.

Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.

Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.