Table 4B.

Relationship between contractile function, cardiac biomarkers, QTc interval and myocyte injury in NHP treated chronically with Vehicle.

NHP#	Dose (mg/kg)	Telemetry unit type	Functional effect or endpoint impacted*
			dP/dT Max	EF	QTc interval	cTnI	NT-pro-BNP	Cardiac injury
104916	0	BP + LVP						(S)
104917	0	BP + LVP						(S)
104918	0	BP + LVP						(S)
104919	0	BP + LVP						(S)
104920	0	BP + LVP						(S)
104921	0	BP	ND					(S)
104922	0	BP	ND					(S)
104923	0	BP	ND		ND			(S)
104924	0	BP	ND					(S)
104925	0	BP	ND					(S)
104926	0	BP	ND					(S)
104927	0	BP	ND					(S)

^*Cardiac contractility (dP/dtmax derived from LVP): >10% reduction = red; no effect (<10%) = green. Ejection fraction (EF): >10% reduction = red; no effect (<10%) = green. QTc interval: >10% prolongation = red; no effect (<10% prolongation) = green. Troponin (cTnI): ≥2 samples with signal (>0.05 ng/ml) = red; 1/0 samples with signal = green. Natriuretic peptide (NT-pro-BNP): ≥2 samples with signal (>0.05 ng/ml) = red; no signal = green; excluded as signal was observed at baseline (pre-dose phase) = gray. Cardiac injury: presence of vacuolation = red; no vacuolation = green.

S, Scheduled sacrifice; U, Unscheduled sacrifice.

ND, not determined due to lack of LVP instrumentation or ECG failure.

No histopathological evidence of cardiac injury was seen in any of the vehicle treated animals and all were sacrificed as scheduled.